7.89J | Fall 2010 | Graduate
Topics in Computational and Systems Biology


Assignments should be typed, with double- or 1.5-line spacing, 12 pt. font and minimum 1" margins (may be printed double-sided)

Written Assignment 1, Due Week #2: What is Computational and Systems Biology?

Students will write a 1-2 page essay explaining their personal definitions of the field(s) of computational and systems biology. The essay should begin with a crisp but comprehensive definition, one or a few sentences in length, set off in italics. Students may choose to define computational biology and systems biology separately or together as seems appropriate. The definition should be original, though may be adapted from someone else’s published definition provided that the source is cited.

Students should illustrate their definitions using as examples 2 or more carefully chosen papers from Week #1-2 of this course, from other papers posted on the course Web site, or from other papers they have read, explaining how the papers fit (or fail to fit) their definition. Generally speaking, those papers that are at or near the boundary of the definition are likely to be most helpful in illustrating the scope of the definition, though papers which are prototypical of the definition or prototypical of a neighboring field may also be helpful. Be sure to cite at least 2-3 references and give full citations at the end (authors, year, title, journal, volume, pages).

Note: There are no right or wrong definitions. Grading of the assignment will be based on the logic, clarity and quality of the student’s writing.

Background information for Written Assignments 2 & 3:

Written assignments 2 and 3 will be geared towards practicing the writing of research proposals. Writing a fellowship proposal serves at least two useful purposes:

  1. if successful, it can lead to funding to support your research, and can be a strong addition to your resume;
  2. it can help you to think critically and creatively about possible research directions in a particular field, and to plan your own research efforts.

Even if not submitted to a funding agency or submitted but not funded, writing a graduate fellowship proposal is also good practice for future writing of postdoc fellowship and research grant applications, etc. For this exercise, students will follow the guidelines of the National Science Foundation Graduate Research Fellowship Program (GRFP), one of the major sources of fellowships for American graduate students in the sciences and engineering, awarding about 2,000 fellowships annually (for a three-year term), with due dates in early November. Although this program is only available to “beginning” graduate students (normally interpreted as prospective or first-year at the time of application, though some exceptions apply) who are US nationals, a variety of international fellowship programs have similar application requirements.

Three 2-page essays form the core of an NSF GRFP application: a Personal Statement, a Previous Research Experience essay, and a Proposed Plan of Research (PPR) essay. We will focus on the PPR in this course.

As background, links to the “Program Announcement” and “Applicant User Guide” are available on the left hand side of the FastLane Graduate Research Fellowship Program (GRFP) web site.

For general advice on preparing an NSF predoctoral fellowship proposal, you may also want to take a look at the Guide to applying for the NSF predoctoral fellowship, developed at Johns Hopkins.

Written Assignment 2, Due Week #3: Initial Idea for Graduate Research Fellowship Proposal

For this assignment, students will draft an initial idea for a proposal (which they can change later if they wish). Think of a topic that interests you and develop a hypothesis related to this topic and a specific aim addressing your hypothesis that could be tested during the course of your Ph.D. You may wish to use the papers we have read or will read in the class for inspiration. If you prefer to choose a different topic, that is fine too. It is also recommended (but not required) that students choose a topic they are genuinely interested in pursuing, or are thinking seriously about pursuing, during their Ph.D.

The Initial Idea Document (double spaced hardcopy printout, 12 point font, with 1" margins), should contain the following:

Student’s Name
Title of Proposal (one line of text max)
Background (50-150 words)
Hypothesis (1 or 2 sentences)
Specific Aim (1 or 2 sentences)
References (3-5 suggested. List authors, year, title of paper, title of journal, etc.)

For example, reading the Alizadeh, et al. paper from Week 3 made student X more certain than ever that he wanted to work on cancer classification and diagnosis using molecular approaches during his Ph.D. After doing some reading, X decided that ovarian cancer is an attractive target. Student X’s initial idea statement might look something like this:

Name: X

Title: Development of a molecular classification for ovarian carcinoma

Background: Ovarian carcinoma is the 3rd leading cause of death among women ages X to Y (ref 1). Current diagnostic criteria emphasize morphological features such as … (ref 2). However, there is substantial heterogeneity in rate of tumor growth, metastasis and response to chemotherapy, suggesting the existence of diverse disease types within the current diagnosis of ovarian carcinoma (ref 3). Previous studies have documented molecular heterogeneity within both diffuse large B cell lymphoma and breast cancer (refs 4,5).

Hypothesis: Ovarian carcinoma consists of multiple, molecularly distinct diseases.

Specific Aim: I propose to develop a molecular classification of ovarian cancer by applying molecular profiling of both mRNAs and microRNAs to a panel of ovarian cancer samples and to distinct cell types isolated by laser capture dissection from normal ovary tissue from autopsy or surgical sources, followed by hierarchical clustering. Subclasses identified will be compared in terms of clinical features such as survival and tumor growth rate, and the genes identified will be analyzed by Gene Ontology and … to assess their possible roles in the disease process.


1. Smith and Jones. “Rates of Common Cancers.” Cancer Research 12 (2002): 347-392.

2. …

3. …

4. Alizadeh, A., et al. “Distinct Types of Diffuse Large B-cell Lymphoma Identified by Gene Expression Profiling.” Nature 403 (2000): 503-11.

5. …

Written Assignment 3, Due Week #5: NSF Proposal Assignment

This assignment is to write a proposal following the NSF instructions exactly, including both length and formatting guidelines (which are invariably present in proposal instructions and serve to level the playing field between applications and make it easier for reviewers to read the applications). One additional requirement is that you must include at least one (but not more than three) specific aims in your proposal, at an appropriate place (i.e. after your hypothesis). Your aim(s) should be in bold type, and your hypothesis sentence should be in italics.

NSF instructions related to the PPR Essay can be found in the Applicant User Guide within the FastLane website (click on Prepare Application under the Applicant User Guide, and scroll down to the Proposed Plan of Research section).

The formatting instructions are as follows:

  1. All essays should be written using a 12 point Times New Roman font. Small type size makes it difficult for reviewers to read the application; consequently, the use of small type not in compliance with the application guidelines may be grounds for NSF to return the application without review.
  2. There is a 2-page limit for the Personal Statement, Previous Research Experience, and Proposed Plan of Research essays. There is a 1-page limit for the Eligibility Essay (for those having completed greater than 12 months of graduate study). References and citations are included toward the page limits. All essays should be written using the standard 8.5" x 11" page size with 1 inch margins at top and bottom.
  3. Character spacing should use normal (100%) single-line space option. Do not condense line spacing or reduce the character spacing scale. Adherence to type size, character spacing, and page length is necessary to ensure that no applicant will have an unfair advantage, by using smaller type or line spacing to provide more text in the application.
  4. Images may be included in your essays, however they will be produced only in black and white. All images, footnotes, endnotes, and other citations are included in the 2-page limit.
  5. Prepare your response using a word-processor.

General instructions/advice. Think of a topic that interests you and develop a hypothesis related to this topic and a specific aim addressing your hypothesis that could be tested during the course of your Ph.D. You may use the papers we have read or will read in the class for inspiration, but if you prefer to choose a different topic, that is fine too. It is also recommended (but not required) that you choose a topic that you are genuinely interested in pursuing or are thinking seriously about pursuing during your Ph.D. You may use the same or a similar idea as you proposed in your assignment due 9/24, or a different idea. Choose the idea you feel most strongly about.

For reference, students should also read the NSF Merit Review Criteria.

Additional advice.

  • Make sure your hypothesis is clear. There should be a sentence in your proposal (italicized) beginning “My hypothesis is …” or similar. Make sure it is stated in the form of a hypothesis, not an aim. For this purpose, a reasonable dictionary definition of the word hypothesis is:

A tentative explanation for an observation, phenomenon, or scientific problem that can be tested by further experimentation.

  • Make sure that your aims are appropriately specific. For example,

“To understand the folding of the helix-turn-helix (HTH) class of proteins, focusing on the representative HTH proteins lacR and Cro, using optical tweezers and molecular dynamics simulations”

is better than

“To understand protein folding using a combination of experimental and computational approaches”

  • References should include authors (may use et al. if more than 3), year, title of paper, title of journal, volume and page numbers, e.g.,

1. Smith and Jones. “Rates of Common Cancers.” Cancer Research 12, (2002): 347-392.

Another fellowship that may be of interest to students is the Krell Institute/DOE “Computational Sciences Graduate Fellowship” (CSGF)

Written Assignment 4, Due Week #7: Writing Assignment — Compare and Contrast

Paper 1. Shen-Orr, S. S., R. Milo, S. Mangan, and U. Alon. “Network Motifs in the Transcriptional Regulation Network of Escherichia Coli.Nature Genetics 31 (2002): 64-68.

Paper 2. Ma, W., A. Trusina, H. El-Samad, W. A. Lim, and C. Tang. “Defining Network Topologies that Can Achieve Biochemical Adaptation.Cell 138 (2009): 760-73.

The papers for Week 7 introduce and discuss the concept of “network motifs”. The first paper draws a parallel to the concept of “sequence motifs” from computational and molecular biology. In a short essay 1-2 double-spaced pages in length, compare and contrast these two concepts and their biological and practical significance, mentioning specific examples of each type of motif. Be sure to precisely define both concepts at an appropriate place.