58312110 Seminar - Bioinformatics of Gene Regulation (3 cr)

Structure of the Seminar (spring 2012)

- Seminar is lead by Prof. Esko Ukkonen (esko.ukkonen@cs.helsinki.fi), office D240b

- Technical Assistant (Wiki etc): Jarkko Toivonen, office B212, jarkko.toivonen@cs.helsinki.fi

- Seminar sessions: on Mondays at 14 - 16 in room C220

- Basic material:

1) W. W. Wasserman & A. Sandelin: Applied bioinformatics for the identification of regulatory elements. Nature Reviews - Genetics 5 (April 2004), 276-287.

2) J. Su, S.A. Teichmann & T.A. Down: Assessing computational methods of Cis-Regulatory module prediction. PLoS Computational Biology 6, 12 (Dec 2010), e1001020

To pass the seminar, you need to do the following four tasks:

1. Write a seminar paper on a topic agreed during the first meetings,
2. Review two papers written by other students (a written review plus discussions),
3. Prepare and present two oral presentations and discuss them with the other students (the first talk is a short overview of your topic and the planned paper, the second talk is a full 45 min presentation of your final paper); and
4. Participate actively in the seminar sessions by asking questions, raising discussions on the topic, and reviewing other students' work.

During Period I all students write their papers in English. The length of the paper is about 8-12 pages. The feedback from other students on your paper is given during period II. The papers are then revised, and the oral presentations of the final papers are given in April.

Participants and their topics (from the list below)

Nicole Althermeler Identification of clusters in DNA - two probabilistic model approaches: Cluster-Buster [15] + MSCAN [13]

Hilal Asan Probabilistic methods for detecting regulatory modules: MCAST [14] + Stubb/StubbMS [16]

Virginia Brilhante Identification of OxPhos Regulator Genes by Computational Expression Screening [BNG, NSP]

Jian Hou Predicting cis regulatory modules using comparative methods: CisPlusFinder [21] + EEL [24]

Mohammad Islam Mixture-modeling and HMM approaches to cis regulatory model prediction: CisModule [19] + MultiModule [20]

Anna Kuosmanen Generalizing the Position Weight Matrix: New approaches to modeling Transcription Factor Binding Sites: [SLS] + [S]

Hailin Lei MorphMS [18] + [GL]

Chunxiang Li Identification of regulatory motifs' targets: PhylCRM [29] + CodeFinder [P]

Marcus Söderholm

Topics

[PMP] Pavesi G, Mauri G and Pesole G (2004): In silico representation and discovery of transcription factor binding sites. Briefings in Bioinformatics 5, 3: 217-236.

[STD] Su J, Teichmann SA, Down TA (2010) Assessing Computational Methods of Cis-Regulatory Module Prediction. PLoS Comput Biol 6(12)

[13] Johansson O, Alkema W, Wasserman WW, Lagergren J (2003) Identification of functional clusters of transcription factor binding motifs in genome sequences: the MSCAN algorithm. Bioinformatics 19 Suppl 1: i169--176.

[14] Bailey TL, Noble WS (2003) Searching for statistically significant regulatory modules. Bioinformatics 19 Suppl 2: ii16--25

[15] Frith MC, Li MC, Weng Z (2003) Cluster-Buster: Finding dense clusters of motifs in DNA sequences. Nucleic Acids Res 31: 3666--3668.

[16] Sinha S, van Nimwegen E, Siggia ED (2003) A probabilistic method to detect regulatory modules. Bioinformatics 19 Suppl 1: i292--301.

[18] Sinha S, He X (2007) MORPH: probabilistic alignment combined with hidden Markov models of cis-regulatory modules. PLoS Comput Biol 3: e216.

[19] Zhou Q, Wong WH (2004) CisModule: de novo discovery of cis-regulatory modules by hierarchical mixture modeling. Proc Natl Acad Sci U S A 101: 12114--12119.

[20] Zhou Q, Wong WH (2007) Coupling Hidden Markov Models for the Discovery of Cis-Regulatory Modules in Multiple Species. Ann Appl Stat 1: 36--65.

[21] Pierstorff N, Bergman CM, Wiehe T (2006) Identifying cis-regulatory modules by combining comparative and compositional analysis of DNA. Bioinformatics 22: 2858--2864.

[23] Kolbe D, Taylor J, Elnitski L, Eswara P, Li J, et al. (2004) Regulatory potential scores from genome-wide three-way alignments of human, mouse, and rat. Genome Res 14: 700--707.

[24] Hallikas O, Palin K, Sinjushina N, Rautiainen R, Partanen J, et al. (2006) Genome-wide prediction of mammalian enhancers based on analysis of transcription-factor binding affinity. Cell 124: 47--59.

[28] Chan BY, Kibler D (2005) Using hexamers to predict cis-regulatory motifs in Drosophila. BMC Bioinformatics 6: 262.

[29] Warner JB, Philippakis AA, Jaeger SA, He FS, Lin J, et al. (2008) Systematic identification of mammalian regulatory motifs’ target genes and functions. Nat Methods 5: 347--353.

[S] Siddharthan R (2010) Dinucleotide weight matrices for predicting transcription factor binding sites: generalizing the position weight matrix. PLoS ONE 5,3: e9722

[SLS] Sharon E, Lubliner S, Segal E (2008): A feature-based approach to modeling protein-DNA interactions. PLoS Computational Biology 4, 8: e1000154

[BNG] Baughman J, Nilsson R, Gohil V., et al. (2009): A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis. PLoS Genetics 5, 8: e1000590

[NSP] Nilsson R, Schultz I, Pierce E, et al. (2009): Discovery of genes essential for heme biosynthesis through large-scale gene expression analysis. Cell Metab. 10, 2: 119-130

[P] Philippakis, A.A. et al. Expression-guided in silico evaluation of candidate cis regulatory codes for Drosophila muscle founder cells. PLOS Comput. Biol. 2, e53 (2006).

[GL] Gupta, M & Liu, J S (2005): De novo cis-regulatory module elicitation for eukaryotic genomes. PNAS May 17, 2005, vol. 102, no. 20, 7079--7084

Guidelines for writing your seminar paper

The goal of writing a seminar paper is to learn by experience the process of writing scientific text that is based on the knowledge you can obtain from open sources but that you have to present in your own words. You learn a lot in this process!

It is important to give proper credit to the original inventors of the content by using literature references.

NOTE: You can easily find from internet different guidelines of writing a paper (say 'writing a term paper' to Google).

Guidelines for making your reviews

The goal of writing a review is to give constructive feedback to the author such that he or she can improve the paper. A good review can consider all aspects of the paper starting from the content and organization to the language style, lay-out, grammatical correctness and typing errors.

Content

- Is the level of exposition suitable? Is something important missing? Is something elaborated in too much detail? Does the paper give enough background material such that the content is understandable without reading the references (assuming that the reader has basic knowledge in the field)?

Organization

- Is the content of the paper presented in a natural order (for example, the central concepts should be defined before they are used)? Does the introduction of the paper give a clear picture to the reader of what is going to happen in the paper? Is the exposition consistent throughout?

- Is the list of references adequate? Are literature references used in the text in a proper way?

Language

- Is the message of each sentence clear? Is the usage of language precise and readable? Is the language grammatically correct? Is the spelling of words correct? Is the punctuation correct?

- Is mathematical and other formal notation elegant and consistently used?

Lay-out

- Is the lay-out of the pages of the paper such that it supports readability: good font size (not too small, not too large), good size of figures and diagrams and the embedded text, a suitable amount of material per page, etc?

NOTE: In your review, you should be constructive. This means that when you think that, say, something is missing in the paper, then you should say in the review, what is missing. Or if you think that a sentence is unclear, you should say as precisely as possible what you don't understand in this specific sentence. E.t.c.

NOTE': The detailed comments concerning typos and small local grammatical improvements etc are easiest to make as hand-written markings to a paper copy of the article. You should prepare such a marked copy and give it to the author.

WORK PLAN (tentative)

Jan 23: introductions, organizing the work

Jan 30: organizing (cont.), wikipage, seminar materials

Feb 6: selection of the topics and source materials for each student

Feb 13: fixing the topics per student, re-allocation of topics if necessary

Feb 27:

- short presentations (max 8 minutes, max 2-4 slides!) by each student of the topic area and of the planned content of the seminar report

- nomination of two reviewers for each student

March 19: check-point session: status check; hopefully many full draft seminar papers written and submitted to the wiki for review

March 26: check-point session - second status check; hopefully some more seminar papers submitted; guidelines for review reports

April 2 (no session): HARD DEAD-LINE - your full draft seminar paper must be submitted latest on this day!

April 16 (no session): dead-line for submitting your two REVIEW REPORTS to the seminar wiki

April 18 at 15:30-17: regular session (note the date and time!) - Feed-back to the authors: each reviewer presents his/hers comments to the author (the first reviewer should spend about 5 minutes for giving ORAL REVIEW and the second reviewer may present some additional remarks); both reviewers give to the author the MARKED MANUSCRIPT

April 26 (no session): HARD dead-line for submitting your final seminar paper, revised as suggested by the reviewers

April 30 at 12 -16 in room C220 FINAL SESSION I - presentation of the papers

    12:15 Anna Kuosmanen
    13:15 Hilal Asan
    14:15 Hailin Lei
    15:15 Mohammad Islam

May 7 at 12 - 16 in room C220 FINAL SESSION II - presentations of the papers

    12:15 Nicole Althermeler
    13:15 Chunxiang Li
    14:15 Virginia Brilhante
    15:15 Jian Hou

Students' working areas

Instructions on how to create a link to your pdf file

First log in using the University account and press the edit button
to go to edit mode.

Modify the text "<create here a link to your paper (pdf file)>" next to your
name to a more descriptive name. Then select this piece of text with mouse,
and press the link button (the one with a chain link on it) to make
a link to your document. If you have stored your document somewhere in the Internet,
you can give its URL in the link field. Otherwise you need to upload your
document to the wiki server. You can do this by selecting the attachment
tab. Then select your file using the browse button. Once the file is chosen
click it so it appears in the link-field. Then press OK or equivalent
button.

After any modifications to the wiki page use the save button to store the
new version.

If you have any problems, you can ask Jarkko Toivonen.