Show that you understand the current state of research on your topic.
The length of a research proposal can vary quite a bit. A bachelor’s or master’s thesis proposal can be just a few pages, while proposals for PhD dissertations or research funding are usually much longer and more detailed. Your supervisor can help you determine the best length for your work.
One trick to get started is to think of your proposal’s structure as a shorter version of your thesis or dissertation , only without the results , conclusion and discussion sections.
Download our research proposal template
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Writing a research proposal can be quite challenging, but a good starting point could be to look at some examples. We’ve included a few for you below.
Like your dissertation or thesis, the proposal will usually have a title page that includes:
The first part of your proposal is the initial pitch for your project. Make sure it succinctly explains what you want to do and why.
Your introduction should:
To guide your introduction , include information about:
As you get started, it’s important to demonstrate that you’re familiar with the most important research on your topic. A strong literature review shows your reader that your project has a solid foundation in existing knowledge or theory. It also shows that you’re not simply repeating what other people have already done or said, but rather using existing research as a jumping-off point for your own.
In this section, share exactly how your project will contribute to ongoing conversations in the field by:
Following the literature review, restate your main objectives . This brings the focus back to your own project. Next, your research design or methodology section will describe your overall approach, and the practical steps you will take to answer your research questions.
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To finish your proposal on a strong note, explore the potential implications of your research for your field. Emphasize again what you aim to contribute and why it matters.
For example, your results might have implications for:
Last but not least, your research proposal must include correct citations for every source you have used, compiled in a reference list . To create citations quickly and easily, you can use our free APA citation generator .
Some institutions or funders require a detailed timeline of the project, asking you to forecast what you will do at each stage and how long it may take. While not always required, be sure to check the requirements of your project.
Here’s an example schedule to help you get started. You can also download a template at the button below.
Download our research schedule template
Research phase | Objectives | Deadline |
---|---|---|
1. Background research and literature review | 20th January | |
2. Research design planning | and data analysis methods | 13th February |
3. Data collection and preparation | with selected participants and code interviews | 24th March |
4. Data analysis | of interview transcripts | 22nd April |
5. Writing | 17th June | |
6. Revision | final work | 28th July |
If you are applying for research funding, chances are you will have to include a detailed budget. This shows your estimates of how much each part of your project will cost.
Make sure to check what type of costs the funding body will agree to cover. For each item, include:
To determine your budget, think about:
If you want to know more about the research process , methodology , research bias , or statistics , make sure to check out some of our other articles with explanations and examples.
Methodology
Statistics
Research bias
Once you’ve decided on your research objectives , you need to explain them in your paper, at the end of your problem statement .
Keep your research objectives clear and concise, and use appropriate verbs to accurately convey the work that you will carry out for each one.
I will compare …
A research aim is a broad statement indicating the general purpose of your research project. It should appear in your introduction at the end of your problem statement , before your research objectives.
Research objectives are more specific than your research aim. They indicate the specific ways you’ll address the overarching aim.
A PhD, which is short for philosophiae doctor (doctor of philosophy in Latin), is the highest university degree that can be obtained. In a PhD, students spend 3–5 years writing a dissertation , which aims to make a significant, original contribution to current knowledge.
A PhD is intended to prepare students for a career as a researcher, whether that be in academia, the public sector, or the private sector.
A master’s is a 1- or 2-year graduate degree that can prepare you for a variety of careers.
All master’s involve graduate-level coursework. Some are research-intensive and intend to prepare students for further study in a PhD; these usually require their students to write a master’s thesis . Others focus on professional training for a specific career.
Critical thinking refers to the ability to evaluate information and to be aware of biases or assumptions, including your own.
Like information literacy , it involves evaluating arguments, identifying and solving problems in an objective and systematic way, and clearly communicating your ideas.
The best way to remember the difference between a research plan and a research proposal is that they have fundamentally different audiences. A research plan helps you, the researcher, organize your thoughts. On the other hand, a dissertation proposal or research proposal aims to convince others (e.g., a supervisor, a funding body, or a dissertation committee) that your research topic is relevant and worthy of being conducted.
If you want to cite this source, you can copy and paste the citation or click the “Cite this Scribbr article” button to automatically add the citation to our free Citation Generator.
McCombes, S. & George, T. (2023, November 21). How to Write a Research Proposal | Examples & Templates. Scribbr. Retrieved September 4, 2024, from https://www.scribbr.com/research-process/research-proposal/
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This page provides a comprehensive list of accounting and finance thesis topics designed to assist students in selecting an impactful subject for their thesis. Whether you are pursuing undergraduate, graduate, or postgraduate studies, the diverse array of topics presented here covers a broad spectrum of specialties within the field of accounting and finance. From traditional areas like audit and taxation to emerging fields like fintech and behavioral finance, this collection aims to cater to a variety of research interests and academic requirements. Each category is meticulously curated to inspire innovative thinking and encourage a deeper exploration of both established and contemporary issues in the discipline.
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This comprehensive list of accounting and finance thesis topics has been curated to reflect the latest challenges and emerging trends within the field. Whether you are exploring traditional areas like taxation and corporate finance or delving into the evolving realms of fintech and international finance, these topics are designed to provide a robust foundation for your thesis research. Each category is intended to spark innovative thinking and encourage a deep exploration of issues that are pivotal to the current and future landscape of accounting and finance. By selecting a topic from this extensive collection, students can ensure their research is relevant, timely, and contributes meaningfully to their academic and professional growth in the field of accounting and finance.
Accounting and finance stand as critical pillars in the modern economic and corporate world, guiding everything from daily business operations to global financial strategies. The study of these disciplines is not just about learning to balance books or manage corporate assets; it’s about understanding the forces that drive economic activities and shape financial landscapes. Research in accounting and finance is paramount as it provides the empirical evidence needed to develop robust financial models, innovative management practices, and effective regulatory policies. The relevance of accounting and finance thesis topics is thus foundational to nurturing informed, adept professionals capable of navigating the complexities of financial markets and addressing the challenges of economic flux.
The breadth of accounting and finance thesis topics is indicative of the field’s extensive scope and its significant impact on societal and economic frameworks. Continued research is essential for advancing theoretical foundations and developing practical applications that address both current challenges and future opportunities. This ongoing academic inquiry is crucial for fostering a financial landscape that is not only robust and dynamic but also ethical and sustainable, ensuring that the field of accounting and finance remains at the forefront of economic innovation and societal advancement.
At iResearchNet, we understand the unique challenges and pressures that come with academic thesis writing. Our custom thesis writing services are designed to be a valuable resource for students who are striving for excellence in their academic endeavors. Whether you are tackling complex accounting and finance thesis topics or any other subject, our expert team is here to support you every step of the way, ensuring that your academic journey is smooth and successful.
Choosing iResearchNet for your thesis writing needs ensures a hassle-free and professional experience. With our comprehensive suite of services, you gain access to expertise, personalized support, and guarantees that make your academic journey smoother and more successful. Trust us to help you navigate the complexities of accounting and finance thesis topics or any other academic challenge, empowering you to achieve your academic and career aspirations with confidence and ease.
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Detailed Walkthrough + Free Proposal Template
If you’re getting started crafting your research proposal and are looking for a few examples of research proposals , you’ve come to the right place.
In this video, we walk you through two successful (approved) research proposals , one for a Master’s-level project, and one for a PhD-level dissertation. We also start off by unpacking our free research proposal template and discussing the four core sections of a research proposal, so that you have a clear understanding of the basics before diving into the actual proposals.
If you’re working on a research proposal for a dissertation or thesis, you may also find the following useful:
PS – If you’re working on a dissertation, be sure to also check out our collection of dissertation and thesis examples here .
Research proposal example: frequently asked questions, are the sample proposals real.
Yes. The proposals are real and were approved by the respective universities.
As we discuss in the video, every research proposal will be slightly different, depending on the university’s unique requirements, as well as the nature of the research itself. Therefore, you’ll need to tailor your research proposal to suit your specific context.
You can learn more about the basics of writing a research proposal here .
You can access our free proposal template here .
Yes. There is no cost for the proposal template and you are free to use it as a foundation for your research proposal.
For self-directed learners, our Research Proposal Bootcamp is a great starting point.
For students that want hands-on guidance, our private coaching service is recommended.
This post is an extract from our bestselling short course, Research Proposal Bootcamp . If you want to work smart, you don't want to miss this .
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Table of contents
Accounting might not sound like the world’s most exciting job, but you’d be surprised just how important it is. Every company worth its salt will need a top-shelf accountant, and to become one, you have to go through the necessary academic process. Now, learning to become an accountant is an uphill task, especially when you consider just how many research papers you’ll have to produce throughout your education. Finding the perfect accounting topics for research paper will be quite challenging, even for the most seasoned and well-prepared student.
Theoretically, you can draw inspiration for your accounting research paper topic from anywhere and from anything – but if you’ve ever actually written one, you’ll know that that isn’t the case. Instead, coming up with the topic alone will require extensive research and a lot of time, as a great research paper has to be:
It’s important to note that the quality of your research partially depends on the topic you choose. That means that by picking a good accounting topic (consider broadening it with our top picks of business research topics ), you can practically build your entire paper from there on forth, making the process far, far easier.
Now, to make the entire process that much easier, you can always opt for a research paper topic that someone else has thought of. It’s true, finding original topics can be arduous because as time goes by, the number of research papers done on any given subject keeps growing.
However, human creativity knows no bounds, which is why there will always be plenty of attention-grabbing and original options for you to pick from. To make it that much easier for you, we’ve decided to develop seventy top-tier accounting research paper topic ideas that you can use for your next research paper, which you can find below.
Writing a paper isn’t easy, which is why you might want to consider getting someone else to do it for you. You might be surprised, but most students opt to pay for college papers rather than write the papers themselves.
Academic institutions and colleges tend to stuff your daily schedule with all kinds of things, which means that getting some help with research paper is a smart decision.
A lot of services that promise supposedly well-written papers with fast turnaround times and at a suspiciously low price offer shoddy work. Getting something that isn’t up to standard is only going to hurt you, as you’ll have to create a brand new research paper and on a much tighter schedule.
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An research proposal examples on finance and accounting is a prosaic composition of a small volume and free composition, expressing individual impressions and thoughts on a specific occasion or issue and obviously not claiming a definitive or exhaustive interpretation of the subject.
Some signs of finance and accounting research proposal:
The goal of an research proposal in finance and accounting is to develop such skills as independent creative thinking and writing out your own thoughts.
Writing an research proposal is extremely useful, because it allows the author to learn to clearly and correctly formulate thoughts, structure information, use basic concepts, highlight causal relationships, illustrate experience with relevant examples, and substantiate his conclusions.
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Prepared for: [Client.FirstName] [Client.LastName] [ Client.Company]
Created by: [Sender.FirstName] [Sender.LastName] [ Sender.Company]
[Client.FirstName] [Client.LastName] [Client.Company] [Client.Company.Address]
[Date] [Sender.Company.Address]
Dear [Title] [Client.LastName] ,
Whether your business is new or old, it needs efficient accounting services for growth and sustainability. Having your books in top shape all year round is an achievement that can help your business function smoothly and provide grounds for sound and promising business decisions.
As your accounting needs will continue to grow with your business, it is imperative to pay careful thought to a long term and viable solution for this vital part of your business. By hiring [Sender.Company] to take care of all your accounting needs, you will be ensuring yourself a step in the right direction. By letting us be your professional accountants you will:
Given the opportunity to work for your promising company, we will prove, with our dedication and high performance, that you have purchased peace of mind in the guise of our professional accounting services.
Sincerely, [Sender.Company]
[Sender.FirstName] [Sender.LastName] [Sender.Title]
[[Project.Name]] [Sender.Company]
[ Client.Company] seeks a full review of their historical financial records and future accounting needs.
At the start, our experts carefully review your past records and assess your financial services needs according to the nature of your company and suggest the services model best suited to your requirements. The work plan is finalized only after an initial (and possibly subsequent) extensive consultation with [ Client.Company] . Periodic review of our services and client feedback is an essential feature of our work plan which ensures that we remain an efficient accounting partner for your business.
Accounting is a function that forms the core of any business. Important business decisions rely heavily upon the financial information at all stages of a project, from planning to execution to finalization. Efficient bookkeeping and financial control ensures the company runs smoothly with an eye for growth. Data, statements and projections are all vital financial figures that a business must have on-hand for sound business performance. Operating as a neutral third party, [ Sender.Company] will provide accurate and unbiased data to [Client.Company] .
[Sender.Company] offers proven expertise in areas such as bookkeeping , accounting , and controller services . Bookkeeping includes the day-to-day business transactions like customer payments, bills, invoices, bill payments, disbursements, and withdrawals. We maintain ledgers for Accounts Receivable, Accounts Payable, and cash accounts and produce daily or weekly reports according to the clients’ preference. Payroll and related activities with tax calculation are also part of our portfolio. Our repertoire also includes preparing periodic reports, financial statements, bank reconciliations and taking care of your general accounting needs.
We will keep [ Client.Company] apprised at all stages of our accounting procedures with regular reports for [ Client.Company] ‘s reference and review. All data will be accessible to the client around the clock through dedicated servers using the most modern software and backup facilities. In addition, we also act as business advisors by keeping an eye on the market trends and advising our clients on using the most modern and efficient methods related to accounting and financial reporting.
According to a recent estimate, outsourcing accounting work can reduce your business cost by as much as 30%. Hiring a specialist accounting firm like [ Sender.Company] will not only lower your business costs but will also provides [ Client.Company] with the benefit of an efficient and experienced accountants.
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Name | Price |
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Conversion from [Company.X] to [Sender.Company] | $2500.00 |
Time period covered: JAN 1, 2015 to Present | $500.00 |
Production of Quarterly Reports | $800.00 |
Subtotal | $3800.00 |
Total | $3800.00 |
Name | Price |
Daily Account Reconciliation | $1000.00 |
Bi-Monthly Payroll Services | $600.00 |
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Quarterly Tax Documents | $600.00 |
Quarterly Filings | $300.00 |
Quarterly Reports | $800.00 |
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Year End Summaries | $500.00 |
Year End Tax Filing Summaries | $500.00 |
Employee Benefits Reports Maintenance | $300.00 |
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Setup Total |
Monthly Total |
Quarterly Total |
Yearly Total |
This pricing quote is tentative and subject to change based after the initial assessment of the state of [ Client.Company] ‘s bookkeeping records.
This Accounting Contract ("CONTRACT") is made and entered into by [ Sender.Company] , a duly licensed and certified public accounting firm in the State of California with its principal place of business located at 200 Clock Tower Pl Carmel, California(CA), 93923, and [ Client.Company] , located at 200 Elaine Dr Pleasant Hill, California(CA), 94523, effective on May 12. It shall continue for a period of 2 years or until terminated as provided by this CONTRACT.
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[client.company] ‘s cooperation, limitation of liability, termination.
If to [Client.Company] : [Client.Company.Address] If to [ Sender.Company] : [Sender.Company.Address]
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This sets forth the entire agreement between [ Client.Company] and [ Sender.Company] . None of the terms within this business contract shall be amended, except in writing and signed by both parties.
[Sender.Company]
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[Sender.FirstName] [Sender.LastName]
[Client.Company]
[Client.FirstName] [Client.LastName]
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Introduction.
Volatility is defined as the statistical measurement of the dispersion in a market index considering the returns (Abdalla and Suliman, 2012). The central banks and regulatory authorities of stock exchanges have highly focused on volatility modelling and forecasting by using asset pricing models for measuring risks and using option pricing formulas for maximising returns.
The Black-Scholes model is an option pricing formula that delivers the scope of portfolio management of stocks along with delivering reliable estimates of volatility (Bhowmik & Wang, 2020). The Saudi stock exchange is also known as Tadawul and it was established in 2007. Tadawul has a market cap of SAR 8.23 trillion and its trade volume amounts to SAR 380.89 billion.
The research topic is to conduct an analysis of the impact of financial volatility estimates and option pricing methods on the returns and risk assessment in the Saudi Stock Market.
The research topic has been selected as volatility has become an integral component of the present financial markets and most of the studies conducted by the past authors have focused on the relationship between volatility of the oil prices in Saudi Arabia and the stock prices. This research will evaluate how the estimation of financial volatility along with using option pricing models can be used for increasing the returns in the Saudi stock market along with conducting a financial risk assessment.
This research will provide more information regarding the dependencies among financial volatility and the Saudi Stock Market along with evaluating the significance of forecasting methods for maximizing gains and minimising risk. The research will provide the investors with better decision making parameters considering the alterations in returns due to financial volatility.
This study research aims to evaluate the influence of financial validity extremists and option pricing methods on the returns and risk assessment in the Saudi Stock Market. The research objectives include analysis of the significance of financial volatility modelling and estimates in the Saudi stock market.
The research will also contribute in the domain of option pricing models that can be used for evaluating the risk associated with the stock prices for guiding the decision making of the investors. The present condition of the Saudi stock market along with its dependencies on oil and other commodities will also be evaluated as an objective of this research.
Lastly, the ways in which returns of investment can be maximized in the Saudi stock market by conducting a proper risk assessment by using financial volatility forecasting and option pricing models will also be discussed. This will facilitate the foreign investors to understand the fluctuations in the Saudi stock along with helping the risk manager is and investors to raise awareness about the risk in Tadawul.
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In Saudi Arabia, the volatility of the stock market and the overall financial industry in the last decade was due to the changes in oil prices. However, the BASEL accords were updated to implement BASEL III for improving the banking and financial regulations. The stock prices in the nation have been declining since 2015 due to the fall in the price of crude oil (Kalyanaraman, 2014).
The government of the country has established a model for Vision 2030 by integrating financial forecasting mechanisms to reduce the dependence on oil for the economy (Simmons, 2006). Volatility is desired in the market as stagnant stock prices do not yield any profits. However, high volatility also implies high risk for the security, and it is measured by using variance and standard deviation among the returns from the market index.
The research questions are:
The financial assets have the characteristics of providing returns on the investment but are also susceptible to market risks due to the returns being variable (Black, 1976). The volatility of the assets remains variable, requiring the forecasting of stocks to analyse the market risk involved. Examination of the stock volatility is crucial for minimising the risk and losses while contributing to increasing financial gains.
Option pricing methods refer to the parameter of volatility for evaluating the price of the stocks (Birge and Zhang, 1999). This is beneficial for risk assessment applications and general portfolio management of the stocks. As per Bhowmik & Wang (2020), price volatility estimation enables the financial institutions to become aware of the current volatility value of the assets they are managing and estimating the future values for maximising investors’ returns. According to Lim and Sek (2013), the two methods of determining financial volatility forecasting include using the GARCH and ARMA models.
The purpose of this research is to evaluate the impact of estimating financial volatility and option pricing methods on the return on investments and risk assessment in the Saudi Stock Market. This research will be conducted using the positivism philosophy for using first and information for deriving the findings.
The research will be conducted using an inductive approach and considering an experimental design to establish the linkage among the variables in the research topic (Saunders et al., 2007). The research will be conducted by conducting a semi-structured interview with 10 Saudi stock exchange employees to understand the implications of financial volatility forecasting and option pricing models.
The research limitations include time and budget restrictions that inhibit surveying with the investors in the Saudi Stock exchange.
The research will require 180 days or six months to complete.
The research will be conducted by analysing the data collected from the interview by forming a thematic analysis for evaluating the open-ended responses. Secondary data will also be considered in this research for comparing the findings from the immediate reactions.
This investigation will identify the measures that are best suited for guiding the investors and financial advisors regarding the maximisation of returns and risk minimisation in the Saudi stock market by using financial volatility estimates and option pricing.
Abdalla, S. Z. S. (2012). Modelling Stock Returns Volatility: Empirical Evidence from Saudi Stock Exchange International Research Journal of Finance and Economics, 85, 166-179.
Bhowmik, R., & Wang, S. (2020). Stock Market Volatility and Return Analysis: A Systematic Literature Review. Entropy, 22(5), 522.
Birge, J.R. and Zhang, R.Q., 1999. Risk-neutral option pricing methods for adjusting constrained cash flows. The Engineering Economist , 44 (1), pp.36-49.
Black, F. (1976). Studies of stock market volatility changes. 1976 Proceedings of the American Statistical Association Business and Economic Statistics Section .
Kalyanaraman, L. (2014). Stock market volatility in Saudi Arabia: An application of univariate G.A.R.C.H. model. Asian Social Science, 10 (10), 142.
Lim, C.M. and Sek, S.K., 2013. Comparing the performances of GARCH-type models in capturing the stock market volatility in Malaysia. Procedia Economics and Finance , 5 , pp.478-487.
Saunders, M., Lewis, P.H.I.L.I.P. and Thornhill, A.D.R.I.A.N., 2007. Research methods. Business Students 4th edition Pearson Education Limited, England .
Simmons, M.R., 2006. Twilight in the desert: The coming Saudi oil shock and the world economy. John Wiley & Sons.
How to write a phd dissertation proposal.
To write a Ph.D. dissertation proposal:
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Our academic experts understand how hard it can be to come up with original accounting research paper topics for assignments. Students are often dealing with multiple responsibilities and trying to balance numerous deadlines. Searching the web or class notes takes up a lot of time. Therefore, we have put together our list of 150 accounting research topics that students can choose from or gather inspiration from.
This area of study has tremendous upside as more businesses rely on managerial accountants to bring innovative changes to their organizations. Here is a list of topics for research paper in this area:
The following collection can be considered accounting hot topics because they deal with the issues that are most important to today’s generation of accountants that utilize advanced software to keep businesses successful:
As students advance academically, they may want to consider these topics for research paper to earn higher scores in their classes. Here are some suggestions:
Many accounting topics for research papers need to draw a reader’s attention right from the start. This list of topics is controversial and should accomplish just that:
These accounting paper topics are meant for students that have acquired skills in writing but may not have developed the skills needed to write a top-notch paper quite yet. They should be easy to research given a proper planning period:
Sometimes you need to consider accounting project topics that would be great for numerous situations. You may need to present before a class or write a paper for a discussion panel. These ideas may suit your needs:
Some cost accounting topics are worthy of an audience but need to be completed within a tight deadline. These project ideas are easy to research and can be completed within one week:
This is another area of accounting that has a promising future for small to large businesses. Here are forensic accounting research paper topics you can use if you are interested in this booming segment:
Good accounting thesis topics should mirror personally important issues. Essay ideas should reflect the things you want to learn more about and explore in-depth. Here is a list that may pique your interest:
The following topic ideas delve into some serious issues in accounting and are much more difficult to handle. These should be approached with the utmost academic determination to earn a master’s or a Ph.D.:
If you don’t have enough time to research current topics in accounting, these ideas will help you save time. There are plenty of online resources discussing current issues and you can also find information in the library:
These are the topics you should be considered for a graduate-level course if you want to make a great impression on the professor. Just be sure to do your due diligence and research your selected topic thoroughly:
Topics in accounting are rooted in financial processes that date back centuries. Yet, there are still many innovative ideas that drive business success. Consider these topics for an essay on issues that are current for today’s world:
The next set of topics are great for anyone wanting to combine accounting with technology. We put together this set to generate interest in this area:
These presentation topics cover a wide range of areas that are perfect for diverse interests. At the college level, students must conduct a lot of academic research to guarantee they have all the most relevant information needed to present on a great topic:
What do you think of our accounting research topics? These are available for free and can be shared with other students. If you need a custom list of accounting topics, our academic experts can take your assignment details and provide you with original and simple accounting research topics to facilitate your project and help you earn a top grade. We can also provide you with writing, editing, and proofreading services to ensure your assignment is error-free and gets you the highest score possible.
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An accounting proposal is created as a response to a request for an accounting services proposal or to make bid. It is also used when there is a need to as for funding for something or to convince potential clients to provide financial support to a specific project program. It is very important that the proposal is well-written and convincing because this is how you will persuade people or organizations to believe in your cause. There are actually a lot of sample proposals were you can get help from, which makes writing proposals a bit easier and more convenient. Below are some samples that you might want to check out for help or as sample reference.
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A basic proposal outline is what you need if you are just getting started with writing proposals. Well, you can get a basic proposal just by looking into this simple accounting proposal sample. What’s in it for you? This sample proposal makes a reliable reference to help you write a simple yet detailed proposal of your own. Simple don’t always mean unreliable. It is often even better than other heavily customized proposals that you may find elsewhere.
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This sample proposal includes a letter sample of transmittal, a profile of the proposer, details about independence and licensing, their firm’s qualifications and experience, a summary of the proposer’s qualifications, references, comprehensive dollar bid, etc. It has everything that you need in a good reference material. it will surley be worth yor time checking this sample out.
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Looking for a proposal sample that you can easily modify? Well, you do’t have to look any further because what you are looking for is right in front of you. In this sample, you will see some parts that are highlighted in green or yellow, which indicates that they are important information or you need to supply them with the required information. Every section of the proposal quotation is also written in bold so that they can be easily distinguished from the rest of the texts. Anince it is made available in Word, you will surely find it easy to use.
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Administration, personnel and security costs are just some of the things that are included in an indirect cost. Indirect cost are often referred to as overhead expenses where they are not directly accountable for the costs of a project. This sample indirect cost proposal is a short and simplified version that is used to help expedite related business negotiations. Included in this sample is a sample checklist , an introduction, a certificate of indirect costs, an accountant’s sample report , an accounting system description, an organizational chart, etc.
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An accounting firm proposal is one of the essential tools that an accounting firm must have so that they can introduce the services that they offer to their potential clients and attract more clients to their business. Using a reliable sample will be to your advantage and will help you get ahead of your competition. This sample is basically everything you need to make a convincing proposal that your clients intake will surely love.
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Another sample that you can use as a guide or reference is this accounting services proposal sample. It uses a simple yet professional layout that will surely make you want to read though all of the pages of this eight-paged proposal. The information that you will find here, include the firm’s background and philosophy, engagement approach and strategy, project scheduling and staffing of engagement, engagement fees, and references.
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What is a request for proposal? A request for proposal or RFP is a document that is used to call out to interested organizations or entities to respond to a certain need in the form of a proposal. The request is written by an organization in need, where they provide formatting specifics and other proposal writing details that they want to be followed by interested participants. Checking out this sample will help you further learn about requests for proposals and become familiar with its contents.
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Ai generator.
Whether you are planning to release the next issue of your journal, or you are organizing an academic conference , you are going to need the scholars in the field of concern to submit their original research papers. Instead of emailing all of the academics you know, you can put up a call for research papers on your website, social media pages, and inside universities.
A call for research papers is an invitation for researchers and academics to participate in a gathering of brilliant minds in the field. Interested researchers can express their intent to participate by sending you abstracts of original scholarly articles. If it is for a journal, the articles will be up for peer review. For conferences and workshops, a committee will screen the submissions and send out confirmation emails to the people whose research papers and articles are accepted for presentation. The call can also be an invitation for esteemed academics to speak at the conference.
It wasn’t always that scientific findings were made known outside the academic circle. Communication about scientists’ findings and discoveries were like whispers within the scientific community, available to only the very few. Private entities funded scientific studies and received the results in return. It wasn’t until science-born innovations in the 19th century began to positively impact how people lived that public institutions began sponsoring research studies. With that, research was gaining a wider audience.
Diffusion Of Knowledge
With the realized potential scientific pursuit for future developments, research grants and funding have been made available to studies that align with an entity’s principles and goals. Another catalyst for the exposition of research to the public also occurred in the 19th century. Knowledge was no longer confined within elite circles as industrialization allowed for more inclusive learning, uplifting the literacy of the common man. The interest in science and research increased. By the end of the century, scientific communication exists in publicly accessible mediums for public consumption.
Stewards Of Science
Today, access to research articles and scientific buzz is a lot easier, thanks to a variety of communication media that people can subscribe to. It is our responsibility as an academic institution and scientific organization to keep the lines open between scientific knowledge and society. Media like online and printed journals allow the public to learn about the recent advances in different scientific fields. They also serve as official chatboxes for scientists to discuss with fellow academics the current research projects and happenings in the community. Meanwhile, conferences are a more personal platform for this conversation. These events also allow students to interact with and learn from mentors and veteran scientists.
A call for research, therefore, is more than a formal invitation for scholarly work and participation. It allows for the growth and dissemination of scientific knowledge. After all, it was the availability of knowledge that ignited the masses’ interest in science and research. That raging fire brought us to where we are today. It is beneficial that we keep these learning channels open through the calling for submission of research papers and articles.
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Anyone can announce research paper submissions, but not all of these notices will be well-received. How do you make your bulletin informative and noticeable to your desired audience?
Get creative. No metric imposes a standard paper-and-plain-text format for your announcement. Instead of following the black and white crowd, add color or photos in your poster and online post. A well-made, professional poster will make your announcement appear official and legitimate. This will also give you good quality submissions.
Don’t skimp on the important details. State in your notice the scope and focus of your journal issue or the motive for the call in your conference poster . Elaborate why the research on a topic is timely and relevant, how your institution is related to the issue, and how it will impact society. However, this doesn’t mean that you slap a novel in your notice. Keep the details informative and concise.
Include the contact details, such as phone numbers, email addresses, and websites in your creative poster for a call for research papers. Should there be any questions, people can contact your organization for clarification. Print the submission instructions clearly. This section includes where and when to send the abstracts of the research papers.
You can contact universities and ask if you can post notices inside the campuses. This approach will encourage students to join your event. You should also take advantage of the virality of social media posts. Create a page for your institution and establish a following. Posting in platforms like Facebook costs less money and effort than printing high-resolution posters. One of the determinants of a trustworthy organization is a well-maintained website . Aside from legitimacy, posting notices is also easier and faster.
You can make use of all these tips in your next call for research papers. With the threat of predatory journals that rob from and take advantage of vulnerable researchers, it is worth noting that the quality of your bulletin will significantly influence the quality of research article submissions.
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Nature Communications volume 15 , Article number: 7114 ( 2024 ) Cite this article
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Culturing and genomic sequencing of Mycobacterium tuberculosis (MTB) from tuberculosis (TB) cases is the basis for many research and clinical applications. The alternative, culture-free sequencing from diagnostic samples, is promising but poses challenges to obtain and analyse the MTB genome. Paradoxically, culture is assumed to impose a diversity bottleneck, which, if true, would entail unexplored consequences. To unravel this paradox we generate high-quality genomes of sputum-culture pairs from two different settings after developing a workflow for sequencing from sputum and a tailored bioinformatics analysis. Careful downstream comparisons reveal sources of sputum-culture incongruences due to false positive/negative variation associated with factors like low input MTB DNA or variable genomic depths. After accounting for these factors, contrary to the bottleneck dogma, we identify a 97% variant agreement within sputum-culture pairs, with a high correlation also in the variants’ frequency (0.98). The combined analysis from five different settings and more than 100 available samples shows that our results can be extrapolated to different TB epidemic scenarios, demonstrating that for the cases tested culture accurately mirrors clinical samples.
Introduction.
Mycobacterium tuberculosis (MTB) research from clinical samples usually involves a culturing step to obtain sufficient bacteria for downstream applications, including MTB whole-genome sequencing (WGS) studies. As a consequence, our current knowledge of MTB characteristics, including its biology during infection, evolution, epidemiology, and diagnostics, is largely based on cultured samples 1 , 2 . It has been hypothesised that the cultivation procedure may constrain the genetic diversity of MTB, either by selecting for specific variants more suited to in vitro growth as happens for some drug resistance mutations or lineages 3 , 4 , 5 , or simply due to the bottleneck imposed by the culture inoculum 6 . If true, this could distort our understanding of bacterial diversity, particularly at the within host level and even affect epidemiological and drug resistance inferences that rely on the presence or absence of a few single nucleotide polymorphisms (SNPs). Direct sequencing from clinical samples is an alternative as it could bypass the potential disadvantages of culturing 7 . However, the implementation of culture-free sequencing techniques is challenging due to the complexity of the sample matrix with low amounts of mycobacterial DNA and a mix of contaminants including host genetic material 8 , 9 .
Previous efforts on culture-free genome sequencing have focused on developing new and affordable protocols for MTB culture-free WGS and assessing their reliability for clinical applications, mainly for AMR diagnosis and transmission inference 10 , 11 , 12 , 13 , 14 , 15 . Those studies show contradictory results regarding overall genetic diversity comparison between culture-based and culture-free WGS. Some publications have identified no significant differences 11 , 12 , while others have reported a reduction in genetic diversity when culturing 13 , 16 . These contradictory results probably reflect limitations of the studies, often focused in one single setting and the limited quality of culture-free sequences prevent a proper comparison of genetic diversity between settings. This is specially true to identify low frequency variants which are more likely to suffer from any technical (i.e. sample processing) and analytical limitations 17 . Therefore, the question of whether culture does actually impose such a bottleneck remains largely unsolved despite its importance. The main goal of this work is to determine, in different TB settings, whether culture reflects the original MTB variability present in the diagnostic samples, typically sputum, making the culture a suitable sample for clinical research.
Here we have put together our own comprehensive dataset including samples from two settings differing in tuberculosis (TB) incidence, burden of AMR, and HIV co-infection; and achieving sufficient sequencing depth to properly compare genetic diversity, especially regarding low-frequency variants. We successfully sequence 61 high-quality sputum-culture pairs from Georgia and Mozambique, which are middle- and high- burden TB settings. For the sputa, we implemented a culture-free WGS approach based either in direct (dWGS) or bait-enrichment (eWGS) sequencing, depending on the amount of MTB DNA. In addition we carry out experimental benchmarking to detect major sources of artifactual genetic variation in culture-free approaches. We also reanalyse available datasets 10 , 13 , 16 to generalise our results across settings and sequencing approaches. Importantly, we develop a tailored analysis workflow to address the absence of standardised laboratory protocols and bioinformatic pipelines, carefully considering artefacts beyond the role of potential contaminants in the sample. Our customised workflow is capable of demonstrating that culture accurately reflects sputum diversity in all the evaluated settings, albeit with some individual exceptions. Our results indicate that the current knowledge of M. tuberculosis diversity based on culturing methods is robust, in the scenarios tested, and therefore the genetic diversity observed in culture generally mirrors that present in the diagnostic sample. In addition, we provide in-vitro and in-silico tools to test the correlation in scenarios not contemplated in this work.
Out of the initial 95 sputum-culture pairs available, 80/95 (84.2%) were suitable for WGS since 4/95 (4.2%) cultures did not grow and 11/95 (11.6%) sputa were MTB negative according to qPCR results and %MTB (Cq>35 and <1%MTB). Given their quality, in terms of Cq and %MTB DNA, 48/80 (60%) sputa underwent dWGS and 32/80 (40%) were enriched before sequencing (Fig. 1a ; see Methods). Percentage of MTB was obtained before and after the enrichment step. We observed that sputa with an initial MTB% within 0.5-10% reached 25.5-98.4% after the enrichment, while those containing initially 10-25% of MTB reached more than 90% of MTB (see Methods).
a qPCR Cq vs %MTB. 95 sputa are each one represented by a point. %MTB was obtained by performing a pre-sequencing run in order to determine if each sputum contained enough MTB DNA to be sequenced directly (light purple) or if it required a previous enrichment step (dark purple). Sputum samples in orange were considered negative (Cq>35 and %MTB < 1%). Shape indicates sample origin: triangles for Mozambique, dots for Georgia. Dashed lines represent thresholds to decide which WGS approach to follow, the horizontal line highlights MTB% = 20%, the vertical line highlights Cq = 25. b Mean depth vs coverage. 86 sputa sequenced with enrichment (eWGS, square) or directly (dWGS, diamond). Colour represents the sequencing quality, good quality samples (the ones used for comparison analysis) are in green and bad quality samples in red. The dashed lines represent the coverage and depth cut-off values to consider a good quality sample, the horizontal line highlights a coverage = 0.95 and the vertical line highlights depth = 30X. Source data is provided as a Source Data file.
A total of 19 sputa sequences did not meet the minimum quality criteria (30X depth and 95% coverage) (Fig. 1b ), thus these pairs were excluded from further analysis. The sequencing performance of the remaining 61 pairs was: median depth 48X for eWGS (30-157X), 74X (33-302X) for dWGS and 114X (46-347X) for cultures. Median genome coverage, at a minimum of 20X depth, was above 96% in all sputa and cultures (Table 1 ). See below the samples’ sequencing workflow in the Methods section. All samples’ information is available at Supplementary Data 1 and Supplementary Fig. 1 .
To determine if culture-free sequencing approaches introduced a bias during the variant calling, we compared fixed and low-frequency variants detected in trios of eWGS, dWGS and culture-WGS from the same TB case in three suitable examples. After variant calling, we implemented a “recovery” step in which all variants not passing filters in one sequencing approach, but accurately called in another approach, were re-included or “rescued” in the analysis. Our rationale was that culture-free WGS is performed in samples with low amounts of MTB DNA, hence increasing the chance of variants not passing the filters due to lower sequencing depths. Before applying our customised calling filters, we identified up to 22 variants only detected in eWGS, all of them at low frequencies (median=22%, range=10-54%). Exclusive variants were also detected in dWGS (up to 8) and in culture-WGS (up to 3) but the magnitude of the differences were minor compared to eWGS (Fig. 2a Venn diagrams in blue). We screened manually the discrepant variants in the eWGS approach, and identified that all of them appeared in supplementary alignments (Supplementary Fig. 2 ). A supplementary alignment is a read segment split from the primary read and aligned to a different region of the genome that can produce false positive calls in the variant calling step 18 , 19 . After discarding supplementary alignments, most discrepant SNPs disappeared giving a concordance of 99-100% in the variant calling between the three sequencing approaches (Fig. 2a ).
a Venn diagrams of the comparisons between trios of direct sputum (dWGS), enriched sputum (eWGS), culture WGS. Amount and percentage of exclusive and common variants are denoted. Blue and orange Venn diagrams represent comparisons of variant calls from default unfiltered bams (including supplementary alignments and filtered bams, respectively. b Comparison of the amount of supplementary alignments between direct (sputum dWGS and culture WGS, light purple) and enriched sputum samples (eWGS, dark purple) in all 61 paired-samples. Median (M) and the total amount of samples ( n ) are shown. Asterisk (*) highlights a significant p -value (Wilcox test, p -value = 0.0002049). Data are presented as box-plots: centre line represents the median, upper bound located at 75th percentile, lower bound at 25th percentile, whiskers at minimum and maximum values and the outliers. Each dot represents one sample. c On the left there is the comparison of the discrepant SNPs exclusive in sputum, either dWGS and eWGS, before and after filtering supplementary alignments. Colours stand for variant calls from bams before discarding supplementary alignments (blue) and after discarding them (orange). The x-axis is discontinued. The right part shows the percentage of supplementary alignments in sputum files, either dWGS (light purple) and eWGS (dark purple). Plot c contains 32/61 pairs, the 16 ones containing a higher percentage of supplementary alignments in each eWGS and dWGS. Samples are ordered from the highest to the lowest amount of supplementary alignments. The complete version containing the 61 pairs can be seen in Supplementary Fig. 3 . d Correlation between the percentage of supplementary alignments and the amount of SNPs removed when discarding supplementary alignments from sputum bam files (represented as SNP difference and calculated as follows: discrepant SNPs exclusive in sputum in Default Bams—Filtered Bams). Colours represent whether the sputum samples have been sequenced directly (light purple) or previously enriched (dark purple). Regression lines, Pearson correlation coefficients (one-side) (Corr) and p -values are shown in the plot. Source data are provided as a Source Data file.
The extended analysis of all the 61 sputum-culture pairs demonstrated that overall the 88.5% (307/347) of the discrepant variants between sputa (either eWGS or dWGS) and paired cultures were false positives introduced by supplementary alignments, and these false positive variation was accumulated in 11/61 sputa (taking into account the sputum samples with more than 5 SNPs discarded due to supplementary alignments). Particularly, eWGS sputa accumulated significantly higher false positive variants than dWGS sputa and cultures (Wilcox test, p -value < 0.001, Fig. 2b ) likely due to a higher amount of chimeric reads causing supplementary alignments. After discarding them from the bam files, we identified a mean of 18.3 false positive SNPs (range 0–106 SNPs corresponding to 1–7.4%) per eWGS- culture pair (Fig. 2c , Supplementary Fig. 3 ) whereas, dWGS-culture pairs showed a lower mean value of 0.3 (1–5 SNP corresponding to 0.3–5%) false positive SNPs (Fig. 2c , Supplementary Fig. 3 ). Notably, a high, positive and significant correlation (corr=0.95 [confidence interval: 0.85–0.98], p -value < 0.001) was obtained between supplementary alignments and false positive SNPs for eWGS, whereas, in the case of dWGS, the correlation was lower and with limited impact on variation (Fig. 2d ). Supplementary alignments accounted for only 1.2% of the reads on average (range: 0.2–7.5; dWGS: 1.0%, eWGS: 2.3%), therefore not impacting the depth and genome coverage (Supplementary Data 1 ).
After applying our tailored SNP calling pipeline we evaluated the genetic diversity between sputum and culture. Overall, a mean of 913 (range 770–1063), representing 97% of the total SNPs detected, were common in sputum and culture (Supplementary Fig. 4 ). The SNPs rescued represent approx 3% of total SNPs, with a mean of 24 (range 5–69) (Table 2 ; Fig. 3a ; Supplementary Fig. 5 ). We noticed that rescued SNPs can have an impact, added to that of/in addition to supplementary alignments, when evaluating the correlation between sputum-culture pairs and can affect both sputum and culture estimated diversity. The effect of both supplementary alignments and the rescue step in the total of discrepancies per sample is detailed in Supplementary Fig. 6 . Regarding exclusive variants, we also observed a small proportion of sputum-exclusive SNPs (mean 1, range 0–10) and culture-exclusive (mean 1, range 0–11). In other words, most of the sputum-culture pairs (49/61, 80.3%) did not display any discrepancies in sputum; 9/61 (14.8%) presented 1–5; and only 3/61 (4.9%) had between 5 and 10 sputum-exclusive SNPs (Fig. 3b ).
a Comparison of the amount of common and exclusive variants (Venn diagrams on the left) and comparison of frequency of variants in sputum (dWGS or eWGS) and culture (on the right). Colours represent common or exclusive variants. Percentage of MTB reads in the dWGS is shown above each plot. The complete figures containing the 61 pairs can be seen in Supplementary Fig. 4 and Supplementary Fig. 5 . b Analysis of sputum-exclusive variants in this dataset and published ones. Percentage of pairs in each dataset with 0, 1-5 or more than 5 sputum-exclusive SNPs (all were not fixed variants). Colours represent the dataset. Abbreviations of countries/regions stand for: MZ-Mozambique, GE-Georgia, UK-United Kingdom, LIT-Lituania, SA-South Africa, VLC-Valencia (Spain). c Histogram of the difference of frequency (freq) between variants obtained in sputum versus culture (frequency in sputum - frequency in culture). Colours represent whether the variants are common or exclusive. Percentages of SNPs are shown on the top of the bars. The plot includes the percentage of SNPs that have a frequency difference equal to 0.Total number of variants is shown in grey boxes (n). d Differences of sputum-exclusive SNPs published in the original paper (in blue) versus the ones found by running our pipeline (in orange) for Goig et al. 10 (upper panel) and Nimmo et al. 16 (bottom panel) datasets. Source data are provided as a Source Data file.
It could be argued that culture-free WGS will be more relevant for determining the frequency of SNPs rather than just their presence/absence. The correlation between the frequencies of SNPs observed in both sputum, either dWGS and eWGS, and culture (common SNPs) was 0.98 (0.93–0.99, p -value < 0.001) (Fig. 3a ; Supplementary Fig. 5 ). By going deeper, we observed that most of the common SNPs (98%) had a small frequency difference within both paired samples (median = 0, ranging 0–10%) with higher frequencies in culture than in sputum (Fig. 3c ). To highlight, 83.4% (46445/55700) presented the same frequency in sputum and culture pairs. As expected, these differences were slightly higher for rescued SNPs with 70% of them ranging 0–10% frequency and a 28% ranging 11–30% frequency (Fig. 3c ).
Regarding the exclusive variants, we observed a total of 40 sputum-exclusive SNPs distributed among 12 sputa, with 17 out of 40 (42%) falling within a frequency interval of 30-40%. For those culture-exclusives, which were present in 12 cultures, 73.8% (31/42) were found within a frequency range of 10-20% (Fig. 3c ).
The results for discrepant variants suggest that, in some cases, variants with intermediate frequencies (between 30-80%) in sputum can be missed in culture. In any case, the number of exclusive variants present only in sputum or in cultures were similar and low compared to those commonly called. To highlight, no fixed-SNP (>90% frequency) was detected within them.
Finally, we extended our analysis to publicly available sputum-culture sequencing data from three different clinical settings 10 , 13 , 16 . In those, authors described differences in genetic diversity between sputum and culture pairs. We only analysed those sequences meeting the quality criteria (see Methods) for comparisons. After applying our pipeline, we observed that 88% of pairs differed in less than 5 SNPs (Fig. 3b ), all of them below 90% frequency. These results are very similar to the ones obtained for the dataset generated in this study (samples from Georgia and Mozambique; Fig. 3b ). For those studies with the number of discrepant SNPs available in the publication (Goig et al. 10 and Nimmo et al. 16 ), our pipeline reduces the number of discrepant SNPs from an average of 10.4 SNPs (median 7, range 4–32) to 0 SNPs in all 7/7 sputum-culture pairs of Goig et al. 10 dataset; and from an average of 8.7 SNPs (median 5, range 1–45) to 1 SNPs (median: 0, range 0–7) in 28/32 pairs from Nimmo et al. 16 . dataset (Fig. 3d ). Contrary to the Goig et al. 10 dataset, in three samples of Nimmo et al. 16 . dataset, the number of SNPs did not decrease before and after applying our tailored pipeline, and there was even an increase in one of the pairs. For that sample (RF0003, Fig. 3d ) the number of discrepant SNPs in sputum is higher than for the rest of comparisons.
Overall, the results from our dataset suggest that almost all the genetic variability present in the original sputum is represented by culture both in terms of presence/absence of SNPs but also in terms of SNP frequency correlation within the samples. Re-analysis of available datasets also points to a high sputum-culture concordance after discarding false-positive variants, mostly due to the bioinformatic analysis implemented.
We obtained a 100% concordance between sputum and culture lineage (L) prediction. We identified 31/61 L4 strains (20 from Mozambique and 11 from Georgia) and 16/61 L2 (8 strains from each dataset). The remaining strains from Mozambique belonged to L1 (13/61 samples) and L3 (1/61 sample). Regarding the re-analysed datasets the lineage distribution was 1/52 L1, 12/52 L2, 2/52 L3 and 37/52 L4. Concordance at lower taxonomic levels according to Coll et al. classification 20 was also 100%. Sublineage classification is shown in Supplementary Data 2 .
All the 61 sputum samples matched with their paired cultures when constructing a Maximum likelihood tree (Supplementary Fig. 1 ) obtaining a 0 SNP in all pairs (fixed-SNP > 90% frequency) pairwise distance. Two samples from Mozambique were in the same transmission cluster (measured at a 5 SNP distance cut-off) which was equally detected when culture and sputum genomes were analysed separately.
Regarding AMR-conferring variants, the agreement between the resistance profile predicted in sputum and culture was 100%. We obtained 10/61 pairs with at least one AMR-conferring mutation (6 from Georgia, 4 from Mozambique): 7/10 mono or poly-resistant, 2 MDR and 1 pre-XDR. All these were fixed-SNPs in both sputum and culture. No low-frequency AMR-conferring variants were found. See Supplementary Data 3 for resistance SNPs information. Regarding the re-analysed datasets, we identified 31/52 strains with at least one AMR-conferring mutation in the sputum and the culture. All of them were fSNPs except one from Shockey’s 10 , 13 , 16 dataset (P10) which was a heteroresistant variant present at 70% in both sputum and culture.
In this study, we explore the role of culturing from sputum diagnostic samples as a bottleneck for MTB genetic diversity. In terms of SNPs’ presence/absence, both fixed and minority variants, after comparing the genomic variability, most culture-sputum pairs (91.8%, 56/61) showed a difference of less than 5 (0–3) SNPs. Strikingly, the correlation of the SNPs’ frequencies was very high (0.98, p -value < 0.001). Our findings show that culture mirrors the genetic diversity present in the sputa analysed, considering both the presence/absence of SNPs and their frequencies. We corroborate our results by reanalyzing previously published datasets, suggesting that any apparent contradictions were likely due to differences in bioinformatic pipelines. Importantly, our findings were consistent across the datasets included, encompassing samples from different clinical settings and laboratories.
One key finding of our study was the detection of false-positive variation driven by chimeric reads most likely produced during sample enrichment and library preparation steps. While this is a common issue, we observed that they were significantly higher in the enriched sputa as compared to direct sputa sequenced. The presence of chimeric reads was potentially due to the low concentration of DNA in sputa. Considering that not all DNA was from MTB, the low quantity of target DNA could lead to non-specific amplifications in both library preparation and PCR reactions carried out during the enrichment. Our hypothesis is that such amplifications likely generate chimeric reads, resulting in supplementary alignments during the mapping and, therefore, false variant calls. Furthermore, a high correlation between supplementary alignments and false-positive SNPs was obtained for eWGS sputa, with special impact on those samples with very low MTB DNA to be captured. Importantly, while removing supplementary alignments reduces by more than 80% the discrepant variants in some cases, it has no impact on depth and coverage. However, a more dedicated study of the factors affecting supplementary alignments is warranted as we identify some non-enriched samples with a high number of alignments.
Another source of discrepancies is driven by differences in depth throughout the genome, which is more relevant in culture-free WGS approaches. To solve this, here we implemented a recovery step to rescue the false negative variants present in the sputum or culture. It was observed that the rescued SNPs only make up less than 3% of the total SNPs analysed in the joint dataset. However, because differences between culture and sputum are subtle, they can make a great impact on the interpretation of sputum-culture differences in specific pairs. This phenomenon is more obvious when looking at specific examples like those presented in Fig. 3a . It is worth noting that the absence of culture could have resulted in the oversight of these variants in the sputum, highlighting the critical role of achieving minimum sequencing depths for diversity comparisons. Overall, these findings unequivocally indicate that achieving an accurate representation of the original genetic diversity depends on sequencing depth, appropriate bioinformatic filters and careful post-processing of results.
The main aim of this study was to assess whether culturing distorts the genetic diversity of the bacterial population present in sputum. By performing an enrichment step, we succeed in increasing the MTB DNA by 26.5-fold on average, allowing high-quality sequences of sputa with as low as 1% of MTB DNA, similar to the values obtained by Mann et al. 21 . Since we have not explored the potential of culture-free WGS as a diagnostic tool for TB, we performed as many runs as necessary to achieve sufficient coverage and depth to reach our goal, regardless of the sequencing cost per sample. With this effort we were able to perform culture-free sequencing, with high quality, in 76% (61/80) of diagnostic samples, suggesting that further improvements of the technique will be needed as shown by others 15 . In fact, while previous studies showed that smear-negative and scanty sputa could be enriched and sequenced occasionally 10 , 11 , 12 , 13 , a formal testing of the limit of detection is still needed. Meanwhile, intermediate alternatives like targeted next-generation sequencing tools are finding a room in the TB diagnostics pipelines 22 .
Understanding that the diversity of M. tuberculosis is reflected in both sputum and culture has an impact on TB research, since the overwhelming majority of studies today rely on culture sequencing to assess diversity, even in those cases where surgery 23 or post-mortem 24 samples are interrogated. Our analysis suggests that diversity of the diagnostic sample is well represented in those studies and that substantial variation is not missed in the matching culture. However, as a limitation, in this study we have not been able to analyse the detection of genotypes carrying AMR mutations (or any other mutation) with a fitness cost in culture. Most of our samples are drug susceptible and our analysis has identified only one case of heteroresistance for quinolones which is equally detected in sputum and culture. Thus, the high correlation observed in our sputum-culture pairs may not apply in situations where a subpopulation has a mutation with associated fitness cost. Mutations such as these are known to cause growth delay and affect culture-based diagnostics, particularly in the case of rifampicin-resistance conferring mutations occurring in rpoB 4 , 25 . Similarly, this limitation also applies to cases where lineages with different growth rates coexist, potentially affecting the identification of polyclonal infections, as it has been previously suggested for Lineage 6 and animal strains 5 . Identification of those scenarios requires specific analysis 23 out of the scope of this work. For some cases, particularly in the datasets from Georgia and South Africa 16 , we identified a higher disagreement between sputum and culture. This may be due to the presence of unknown fitness-cost associated mutations or to polyclonal infections with genetically close strains, which are more likely to happen in those settings, particularly if there are high transmission hotspots 26 . Finally, a proportion of non-cultivable bacterial populations in the sputum of patients has been described in some studies, which may be relevant at the clinical level 27 , 28 . In the case that those populations are genotypically different (currently unknown) it may be reflected in the few SNPs and pairs with sputum exclusive SNPs or it may well be a phenomenon occurring below our limit of detection of 10% frequency. Those specific situations remain to be tested and here we provide tools for an accurate assessment of the sputum-culture diversity. Nevertheless, our dataset reflects the reality of many TB cases, which are from single infections and carry drug-resistance mutations that do not cause growth problems in culture.
In conclusion, our results highlight the importance of evaluating and applying appropriate filtering steps when sequencing complex samples, such as sputum, in order to detect and discard sources of false variation. After developing and applying a tailored bioinformatics analysis, we show that culture accurately captures the genetic diversity present in diagnostic samples and this is true across settings and laboratories tested. More specific scenarios remain to be analysed and here we provide laboratory and bioinformatics tools to do so. On one hand, from a diagnostic point of view our results reflect the long road ahead towards whole genome-based diagnostics, as highlighted in recent publications 15 . On the other hand, from a research point of view our results support the large body of work based on culture sequencing.
The samples from Mozambique came from a study that was approved by the National Bioethics Committee for Health of Mozambique (CNBS, Ref:369/CNBS/17) and the Internal Bioethics Committee of CISM. Regarding samples coming from Georgia, the ethical approval was obtained from the Institutional Review board (IRB) of the National Center for Tuberculosis and Lung Diseases within the framework of observational clinical study NCT02715271. All methods were performed in accordance with the relevant guidelines and regulations. An informed consent was signed by all participants after providing a verbal explanation and written information about the study. Regarding participants under 18 years of age, the informed consent was obtained from their relatives (parents or guardians). All data were de-identified before the analysis.
We received sputum-culture paired samples from the Centro de Investigação em Saúde de Manhiça (Mozambique) and the National centre for Tuberculosis and Lung Diseases located in Tbilisi (Georgia). Mozambique and Georgia are considered high- and medium- burden tuberculosis countries. No statistical method was used to predetermine sample size. To ensure that the bacillary load present in sputum samples was enough for sequencing, we selected 50 sputum samples from Mozambique graded High/Medium according XpertUltra result and 3+/2+ according to smear microscopy result. Regarding Georgia, we processed all 45 sputum samples received due to the lack of bacillary load information. In summary, we processed 95 sputum-culture paired samples.
Sputum samples, collected at diagnosis, were homogenised and decontaminated in origin countries. In Mozambique, they performed the N-acetyl-L-Cysteine-sodium hydroxide (NALC-NaOH) or Kubica method 29 , while in Georgia they followed the modified Petroff protocol, that uses 4% NaOH, which was validated under supervision of the WHO Supranational TB Reference Laboratory in Antwerp 30 .
The paired cultures were grown in 7H11 solid media, supplemented with OADC and glycerol to ensure a high amount of bacteria for sequencing.
All samples, cultures and sputa, were received and processed at FISABIO biosafety level 3 (BSL-3) facilities in Valencia, Spain.
Dna extraction from sputum samples.
DNA extraction from sputum leftovers was based on a differential cell lysis procedure to remove non-MTB contaminant DNA using MolYsis basic5 kit (Molzym, Germany). We followed a modified version of the original protocol that entailed an initial lysis of non-mycobacterial cells to remove contaminant DNA, followed by an inactivation of MTB cells at 95 °C for 15 min and a mechanical cell disruption using FastPrep. DNA precipitation steps were performed using ethanol, sodium acetate and Glycoblue. DNA extraction steps are detailed as follows:
Saline wash
Centrifuge 1 mL of sample at 13,000 rpm during 15 min
Remove supernatant by pipetting without disturbing the pellet (leave 200uL of liquid)
Add 1 mL of PBS and resuspend the pellet by pipetting.
Lysis of human cells with MolYsis Basic5 kit:
Add 250 µL of CM buffer, mix by slow pipetting
Incubate 5 min at room temperature (Note: CM is a chaotropic buffer)
Add 250 µl buffer DB1 and 10 µl MolDNase B (do not premix) to each sample and immediately vortex for 15 s.
Incubate at room temperature for 15 min.
Centrifuge the tubes at 13,000 rpm for 10 min.
Discard the supernatant taking care to not disturb the pellet.
Add 1 mL of RS buffer and pipette up and down until the pellet is resuspended.
Centrifuge the tubes at 13,000 rpm for 10 min (During this step, set a thermal block to 95 °C for MTB inactivation.
Add 700uL of sterile mqH2O and resuspend the pellet by pipetting up and down.
MTB Cells Inactivation:
Spin down tubes at maximum speed 30 s and incubate at 95 °C for 15 min.
Mechanical cell disruption
Transfer all the volume 700uL to a 2 mL FastPrep Lysing Matrix B tube.
Break the cells using the FastPrep Mycobacterium tuberculosis program using 1 pulse instead of two (45 s at 6.5 m/s). Microscopic glass beads break the mycobacterial cell.
Spin the tubes in the centrifuge and transfer 450 uL to a new microcentrifuge tube.
DNA ethanol precipitation procedure:
Add 1/10 vols (45ul) of sodium acetate 3 M to the supernatant.
Add 1.5ul of GlycoBlue.
Add 2 vol (1000 μl) of cold EtOH 96% and vortex 10 s.
Incubate at −20 °C for 30–60 min.
Centrifuge at 13,000 rpm or maximum speed for 15 min and remove the supernatant leaving a small volume of liquid to not disturb the pellet.
Add 1 ml of EtOH 70% centrifuge at maximum speed for 5 min and remove the ethanol without disturbing the pellet.
Let the ethanol dry (but not overdry), preferably in a vacuum centrifuge machine.
Resuspend the pellet in 50 μl of Tris-Hcl 10 mM and dissolve the DNA by pipetting up and down.
Cultures were heat inactivated at 90 °C during 30 min and then MTB DNA was extracted following the standardised CTAB protocol 31 based on an overnight cell wall digestion with lysozyme, followed by incubation steps with proteinaseK, SDS, CTAB and NaCl and a final DNA precipitation step with isopropanol. All bacterial cultures and DNA extraction steps were performed in a BSL-3 laboratory.
We assess the concentration of MTB in sputum samples to decide the sequencing approach. The qPCR was performed in a total volume of 20 μL including 10 μL of Kapa Fast Probe Master Mix 2X, 2 μL of forward and reverse primers mix 2.5 μM, 0.6 μL of probe 10 μM; and 1 ng of DNA. We used DNA normalised to 0.5 ng/μL. The qPCR assay consisted on the amplification of a 65 bp region within the Rv2341 gene using the following primers: Forward-GCCGCTCATGCTCCTTGGAT, Reverse-AGGTCGGTTCGCTGGTCTTG, Probe-TGAGTGCCTGCGGCCGCAGCGC 32 .
We prepared NexteraXT (Illumina) libraries for all samples. Libraries from cultures were sequenced directly. Regarding sputum samples, we classified libraries for dWGS (direct) or eWGS (enriched) depending on Cq and %TB obtained in pre-sequencing runs as described in ref. 10 . Therefore, we performed a qPCR targeting Rv2341 gene 10 , 32 to quantify the amount of MTB DNA. Sputa that obtained a Cq value above 35 (equivalent to less than 2 genome copies) were considered negative (not suitable for sequencing) (See qPCR conditions section). Libraries were prepared for all MTB positive samples (Cq<35) and a pre-sequencing run was performed to estimate the percentage of MTB. According to qPCR and pre-sequencing %MTB result we performed dWGS in sputa obtaining a Cq<25 and more than 20% of MTB and the rest sputum samples underwent an enrichment step before sequencing. The enrichment step consisted of a MTB DNA capture using RNA biotinylated baits (See Enrichment step section). See the flowchart in Fig. 4 .
Diagram summarising the sequencing steps and the amount of samples that have passed or have been discarded (in red). Abbreviations: C-Culture, S-Sputum, P-Pair, dWGS-sputum samples not enriched, eWGS-sputum samples enriched.
WGS was performed in Illumina Miseq (2x300bp) or NextSeq (2x150bp) platforms. Samples were sequenced until a minimum of 30X median depth was reached.
We used myBaits kit (Arbor Biosciences) to perform the hybridisation MTB DNA capture step following the myBaits protocol Version 4.01. This protocol is based on a hybridization of already prepared whole genome sequencing libraries (prepared using NexteraXT kit, Illumina) with RNA biotinylated baits at 65 °C overnight (at least 24 h). During this step, baits hybridised to denatured MTB DNA. Then, most non-captured DNA is discarded by different cleaning steps with streptavidin-coated magnetic beads. Finally, the MTB library is amplified by a post-capture PCR in a 50uL reaction containing 25uL of KAPA HiFi HotStart ReadyMix PCR Kit (Roche), 200 nM of Illumina sequencing primers P5 and P7; and 15uL of captured library. Post-capture PRC conditions are the following: 15 cycles of 20 s to 98 °C, 30 s to 65 °C and 1 min to 72 °C.
The RNA-biotinylated baits panel was designed and developed by Arbor Biosciences using as reference the inferred ancestor genome of the MTB (NC_000962.3), genetically equidistant to all the MTB lineages. This panel is available upon request.
We evaluated the enrichment step by obtaining the fold-change of the percentage of MTB reads between the 32 sputum samples before and after the enrichment. The median fold-change was 10.96 (Fig. 5 ). In other words, sputa containing an initial MTB% within 0.5–10% got a 64.8% (average) while those with an initial MTB% of 10–25% reached 94.3% after undergoing the enrichment step (Fig. 5 ).
Comparison of %MTB DNA before and after the enrichment step of the 32 sputum samples that have been enriched. Each point represents a sputum sample. Colours represent samples’ origin orange for samples from Georgia and purple for samples for Mozambique. Lines link each sputum sample before and after the enrichment. Source data are provided as a Source Data file.
Core analysis.
Analysis was performed using our routine pipeline available at https://gitlab.com/tbgenomicsunit/ThePipeline for both culture and sputum samples. First, reads were trimmed by quality with FastP 33 ; non-MTB reads were discarded using Kraken (v0.10.5) 8 , 34 . MTB reads were mapped to the reference ancestor genome (NC_000962.3) 35 , which is genetically equidistant to all lineages, using BWA (version 0.7.10-r789) 18 .
Samples with a median depth below 30X and less than 95% of the genome covered were discarded for downstream variant comparison analysis. For the remaining good quality samples, variants were called with VarScan (version 2.3.7) 36 and Samtools v1.15 37 by applying stricter coverage and frequency filters for culture samples than for sputum samples (variants called in at least 3 reads, in both strands for sputum; variants appearing in 6 reads, in at 10X depth and in both strands, for culture) (see parameters for VarScan in Fig. 6 ). For the genetic diversity comparison analysis, we discarded SNPs appearing in high density regions with GATK (version 4.0.2.1) 38 or genomic regions that are known to be challenging for short-read mapping such as repetitive genes or mobile elements (PE/PPE gene families) 39 by using a customised Python2 (version 2.7.5) script. Highly conserved genes such as rrs and rrl were also discarded for the comparisons to avoid false positive variability coming from non-MTB reads not discarded by Kraken. We also obtained Pearson’s correlation of the variant frequency obtained in each sputum-culture pair (the mean, median and the range).
Fixed SNPs (fSNPs) are the ones called at a frequency above 90%. After obtaining SNP files additional filters were applied as described in the Core analysis section.
To investigate if the capture step introduced bias in variant calling, we analysed sputum samples sequenced by direct (dWGS) and enrichment (eWGS) methods and compared to the respective culture (hereafter, trios-analysis). All discrepant positions within trios, but particularly between eWGS and dGWS samples, were manually checked on the reads alignment to the reference genome in Tablet viewer (v1.17.08.17, see Supplementary Fig. 2 ) to identify the causes of the inconsistency. All discrepant variants were identified in supplementary alignments, which are part of a read that is split and aligned to a different part of the genome than the primary alignment 18 , 19 , were identified as the main source of false positive variants. Therefore, we discarded them from bam files running samtools v1.15 (command: samtools view -bh -f0 -F256 -F2048 $BAM_FILE), before variant calling step. Afterwards, we evaluated the impact of discarding supplementary alignments in diversity comparison in all the 61 pairs (sputum-culture) analysed.
After applying all filters described above, a pairwise comparison of variants was conducted within sputum samples and their corresponding cultures. At this point we included a recovery step based on searching for the discrepant SNPs, in the files of the paired sample obtained from a less restrictive variant calling. The reason was that in samples with suboptimal depth the missing SNP may still exist but may have been lost during the filtering steps. Parameters used in VarScan pileup2snp for generating rescued SNP files for comparison analysis were: --min-coverage 2, --min-reads2 1, --min-freq-for-hom 0.9, --min-var-freq 0.01.
The average of rescued SNP shared within sputum and culture pairs was 24 (5–69) representing the 2.5% (0.5–7.9%) of the total variants, highlighting the importance of the step when dealing with samples of heterogeneous coverage.
To verify if rescue was biassing the comparison analysis, we conducted a concordance analysis to corroborate that our rescue approach was not artificially removing true discrepant positions. We analysed 35 sputum-culture pairs with depth of coverage >50x and >95% of the genome covered by applying the same calling pipeline (see the variant calling parameters for cultures in Fig. 6 ) and skipping the rescue step. Results showed a median of 886 (range: 828–1059) of common variants, 2 (range: 0–6) sputum-exclusive variants and 2 (range: 0–16) culture-exclusive variants. This corresponded to a median Cohen’s Kappa coefficient 40 of 0.998 (0.992-1) which represented an almost perfect agreement. In this case, the median Pearson’s correlation of variants frequencies was 0.939 (0.454–0.991).
Finally, variants appearing in both samples were classified as “common”, variants rescued were classified as “common rescued”, sputum-exclusive variants were called “only sputum” and those culture-exclusive were classified as “only culture”.
We applied our pipeline described to analyse genetic variability on available sputum-culture paired data sets. We downloaded the sequences under the following project accession numbers from ENA: PRJEB9206 12 , PRJNA486713 16 and PRJEB37609 10 . Sequences were analysed and only pairs passing the quality filters were compared as explained above (see Bioinformatic Analysis from Methods).
The resistance profile was obtained by looking for DR-conferring mutations (>10% frequency) listed in the WHO catalogue (version from 03/09/2021) 41 . Lineage and sublineage classification of the strains was determined by looking for phylogenetic variants reported in bibliography 20 , 42 .
Overall, even though the sequencing quality for some sputum was not enough for the comparison analysis, we were able to classify phylogenetically 74/80 (92.5%) sputum samples sequenced and 72/80 (90.0%) at a sublineage level according Coll et al. classification 20 .
Pairwise distance between each sputum-culture pair was obtained using the R package ape 43 based on a multiple alignment of fixed SNPs (fSNPs, >90% frequency). In addition, we also obtained the pairwise distance to see whether paired samples clustered together. Neighbour joining trees were constructed using MEGA version X 44 .
Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.
Sequences generated in this paper have been deposited in the European Nucleotide Archive (ENA) under project accession number: PRJEB64897. Detailed information about the samples can be found at Supplementary Data 1 . We also downloaded the sequences under the following project accession numbers from ENA: PRJEB9206 ( https://doi.org/10.1128/jcm.00486-15 ) 12 , PRJNA486713 ( https://doi.org/10.1186/s12864-019-5782-2 ) 16 and PRJEB37609 ( https://doi.org/10.1016/S2666-5247(20)30060-4 ) 10 . Source data are provided with this paper.
The pipeline used for analysing sputum and culture sequences has been developed and validated in our laboratory and it is available at: https://gitlab.com/tbgenomicsunit/ThePipeline .
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This work has been supported by the following: European Research Council (ERC): H2020-ERC-COG/0800; Ministerio Español de Ciencia e Innovación: PID2022-137607OB-I00 and Fundació La Caixa: HR21-00415 received by I.C; Stop TB partnership (TB REACH): STBP/TBREACH/GSA/W5-30 received by A.G.B; and International Science and Technology Center (ISTC): Project #G-2143; National Institute of Allergy and Infectious Diseases (NIH) received by N.S. We would like to thank Katharine Walter for reviewing the manuscript and providing her feedback.
These authors jointly supervised this work: Mariana G. López, Iñaki Comas.
Instituto de Biomedicina de Valencia, IBV, CSIC, València, Spain
Carla Mariner-Llicer, Manuela Torres-Puente, Mariana G. López & Iñaki Comas
University of Basel, Basel, Switzerland
Galo A. Goig
Swiss Tropical and Public Health Institute, Allschwil, Switzerland
National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia
Sergo Vashakidze, Iza Khurtsilava, Zaza Avaliani, Marika Shurgaia & Natalia Shubladze
The University of Georgia, Tbilisi, Georgia
Sergo Vashakidze
FISABIO, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, València, Spain
Luis M. Villamayor
ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
Belén Saavedra-Cervera & Alberto L. García-Basteiro
Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique
Belén Saavedra-Cervera, Edson Mambuque & Alberto L. García-Basteiro
Wellcome Sanger Institute, Hinxton, UK
Belén Saavedra-Cervera
European University, Tbilisi, Georgia
Zaza Avaliani
Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA
Alex Rosenthal & Andrei Gabrielian
CIBERINFEC, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Barcelona, Spain
Alberto L. García-Basteiro
CIBERESP, Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública, Madrid, Spain
Iñaki Comas
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A.G.B., B.S.C. and E.M. were responsible for data and samples collection in Mozambique. S.V., I.K., Z.A., A.R., A.G., M.S. and N.S. were responsible for data and samples collection in Georgia. C.M.L., M.T.P., L.V. processed and sequenced the samples. M.T.P., M.G. and I.C. conceived and designed the experiments. C.M.L., M.G. and I.C. were involved in data interpretation. C.M.L., G.G., M.G. and I.C. wrote the paper. All the authors reviewed and approved the manuscript for submission.
Correspondence to Mariana G. López or Iñaki Comas .
Competing interests.
The authors declare no competing interests.
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Nature Communications thanks Maha Farhat who co-reviewed with Brendon Mann; Conor Meehan and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. A peer review file is available.
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Mariner-Llicer, C., Goig, G.A., Torres-Puente, M. et al. Genetic diversity within diagnostic sputum samples is mirrored in the culture of Mycobacterium tuberculosis across different settings. Nat Commun 15 , 7114 (2024). https://doi.org/10.1038/s41467-024-51266-0
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BUSINESS - COMPARATIVE ANALYSIS OF THE PROFITABILITY OF ETIHAD AIRWAYS IN 2013 AND 2014. Introduction. This proposal will discuss the research topic, questions, and objectives. It will also include the methodology of the research, and the work plan which is designed to guide and track the organization of the research.
A research proposal submitted in the SCH OF ACCOUNTING AND FINANCE OF NKUMBA UNIVERSITY . × ... Conceptual Framework 12 CHAPTER THREE 14 METHODOLOGY 14 3.0 Introduction 14 3.1 Research design. 14 3.2 Research Population. 14 3.3 Sample size 14 Table1. Population and sample size table. 15 3.4 Sampling procedures 15 3.5 Research Instruments 16 3. ...
17 Research Proposal Examples. Written by Chris Drew (PhD) | January 12, 2024. A research proposal systematically and transparently outlines a proposed research project. The purpose of a research proposal is to demonstrate a project's viability and the researcher's preparedness to conduct an academic study.
10 Research Title for Accounting Students. "Navigating Financial Reporting Challenges in the Era of Digital Transformation". "Ethical Dilemmas in Corporate Financial Decision-Making: A Comprehensive Analysis". "Unlocking the Potential of Data Analytics in Auditing Processes".
This review of accounting education literature includes 223 articles published over a three-year period, 2003-2005, in five journals: Journal of Accounting Education, Issues in Accounting ...
A Resource Guide to Accounting Information! How to Write Good Research Proposal Examples | Thesis Writing Tips, Thesis Topics and Sample Theses.
Research proposal examples. Writing a research proposal can be quite challenging, but a good starting point could be to look at some examples. We've included a few for you below. Example research proposal #1: "A Conceptual Framework for Scheduling Constraint Management".
Taxation Thesis Topics. 1. Accounting Thesis Topics. The impact of artificial intelligence on financial reporting and compliance. Blockchain technology in accounting: disrupting traditional processes. The role of ethical leadership in promoting sustainable accounting practices.
Accounting Dissertations Daniel L. Jensen,1982. Accountancy Ph. D. Program University of Illinois at Urbana-Champaign. Department of Accountancy,1989 Research Methods in Accounting Malcolm Smith,2014-10-27 Designed solely for accounting students and scholars, this easy-to-follow and engaging text will ensure that you can successfully apply the ...
Figures. .2: North American academic accounting journals. …. .4: Outline headings for critique of academic article. …. .2: Examples of dissertation titles. …. 1 shows some of the main ...
Research Proposal Example/Sample. Detailed Walkthrough + Free Proposal Template. If you're getting started crafting your research proposal and are looking for a few examples of research proposals, you've come to the right place. In this video, we walk you through two successful (approved) research proposals, one for a Master's-level ...
Style: If space allows, provide a clear project title. Structure your text - if allowed use section headings. Present the information in short paragraphs rather than a solid block of text. Write short sentences. If allowed, provide images/charts/diagrams to help break up the text.
Group proposal templates will help you create the perfect group proposal when you need to submit them as a group. 3. Present a timeline or a time frame that you will follow when it comes to providing your accounting services. The time duration that you will specify should be realistic for goals to be attainable.
Sample Research Proposal In Accounting And Finance Nigel Finch,Tyrone M. Carlin The Real Life Guide to Accounting Research Christopher Humphrey,Bill H.K. Lee,2004-04-06 The Real Life Guide to Accounting Research goes behind the more official presentations and accounts of research methods to explore the lived
Table of contents. 1 Interesting Accounting Research Paper Topics. 2 Financial Accounting Research Topics. 3 Auditing and Assurance Research Topics. 4 Taxation Research Topics. 5 Simple Accounting Research Topics. 6 Advanced Topics for Accounting Research. 7 Forensic Accounting Research Paper Topics. 8 Managerial Accounting Research Paper Topics.
An research proposal examples on finance and accounting is a prosaic composition of a small volume and free composition, expressing individual impressions and thoughts on a specific occasion or issue and obviously not claiming a definitive or exhaustive interpretation of the subject. Some signs of finance and accounting research proposal:
The first objective of our study is to examine whether or not the manufacturing sector has acted as an engine of growth for the major Indian states. For this we require data on growth of manufacturing output and net state domestic product (NSDP) for the period 1994-95 to 2005-06. We will consider output for the overall manufacturing sector ...
Objective. Accounting is a function that forms the core of any business. Important business decisions rely heavily upon the financial information at all stages of a project, from planning to execution to finalization. Efficient bookkeeping and financial control ensures the company runs smoothly with an eye for growth.
Sample PHD Finance and Accounting Dissertation Proposal. Here is a sample that showcases why we are one of the world's leading academic writing firms. This assignment was created by one of our expert academic writers and demonstrated the highest academic quality. Place your order today to achieve academic greatness.
BA in Accounting Research Proposal - Free download as PDF File (.pdf), Text File (.txt) or read online for free. This document proposes a case study on the impact of financial accounting reporting on the performance of Rift Valley University, Adam Branch. It will examine the university's financial accounting records, including the general journal, source documents, ledgers, classification of ...
Here are forensic accounting research paper topics you can use if you are interested in this booming segment: Methods for identifying instances of money laundering. The government's right to search private accounts. The use of tax records to report possible crimes. Class action litigation cases in the United States.
Research Proposal Template; Non Resident PhD; Graduate Studies Navigation. Sitemap. Home; About Us. Committee Papers; Annual Report; Awards. Trinity Research Doctorate Group-Based Awards. Group Based Award Winners 2024-25; Group Based Award Winners 2023-24; Trinity Research Doctorate PI-Based Awards.
Sample Research Proposal - Free download as PDF File (.pdf), Text File (.txt) or read online for free. This research proposal aims to assess the qualities and preparedness of 4th year accountancy students at Emilio Aguinaldo College in Manila. The study will evaluate factors like students' entrance exam scores, grades in accounting subjects, and profiles that may affect academic performance.
Sample Independent Audit & Accounting Services Proposal Template. fresnolafco.org. Details. File Format. PDF. Size: 465 KB. Download. This sample proposal includes a letter sample of transmittal, a profile of the proposer, details about independence and licensing, their firm's qualifications and experience, a summary of the proposer's ...
10+ Call for Research Examples. A call for research, therefore, is more than a formal invitation for scholarly work and participation. It allows for the growth and dissemination of scientific knowledge. After all, it was the availability of knowledge that ignited the masses' interest in science and research.
After accounting for these factors, contrary to the bottleneck dogma, we identify a 97% variant agreement within sputum-culture pairs, with a high correlation also in the variants' frequency (0. ...