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  CSE 590CSp '08:  Reading & Research in Comp. Bio.
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 Course Info    CSE 590C is a weekly seminar on Readings and Research in Computational Biology, open to all graduate students in computational, biological, and mathematical sciences.
When/Where:  Mondays, 3:30 - 4:50, EEB 025 (schematic)
Organizers:  Joe Felsenstein, Bill Noble, Larry Ruzzo, Harlan Robins
Credit: 1-3 Variable
Grading: Credit/No Credit. Talk to the organizers if you are unsure of our expectations.
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 Date  Presenters/Participants Topic Details
03/31---- Organizational Meeting ----
04/07Field CadyThermodynamic Error Regulation in Biochemical ReactionsDetails
04/14David Reiss, ISBLearning a predictive model of the transcriptional regulatory dynamics of a free, living cell: Version 2Details
04/21Imran RashidInferring Biological Pathways through Constrained Searching of Molecular Interaction GraphsDetails
04/28Adrienne WangSystematic discovery of vertebrate regulatory elementsDetails
05/05Elizabeth TsengFinding non-coding RNAs through genome-scale clusteringDetails
05/12Harlan Robins, FHCRCTBA 
05/19Robert Gentleman, FHCRCString Matching and Next Generation SequencingDetails
06/02 Special Event:
CMB Symposium
Join us all afternoon in room CSE 403, especially for the keynote at 4:00:
Dr. Joseph Felsenstein, 2008 Darwin-Wallace Medal Winner, ``Developing and distributing a phylogeny package: tales of the PHYLIP''

 Papers, etc.

  Note on Electronic Access to Journals

Links to full papers below are often to journals that require a paid subscription. The UW Library is generally a paid subscriber, and you can freely access these articles if you do so from an on-campus computer. For off-campus access, follow the "[offcampus]" links below or look at the library "proxy server" instructions. You will be prompted for your UW net ID and password once per session.  

03/31: ---- Organizational Meeting ----

04/07: Thermodynamic Error Regulation in Biochemical Reactions -- Field Cady

   Abstract:   It is known that DNA replication has fidelity far above what would be predicted by equilibrium thermodynamics. Attempts to explain the phenomena in terms of reaction rate constants have neglected thermodynamic treatment of the subject. I present a new, stochastic model of replication which shows the critical role of sustained nonequilibrium for reaction fidelity, and shows how the error rate can be modulated in real time. The model constructed is very general, and the mechanism I identify may be widespread in biochemistry.

04/14: Learning a predictive model of the transcriptional regulatory dynamics of a free, living cell: Version 2 -- David Reiss, ISB

   Abstract:   Our group recently published the first draft of a predictive model of the genome-wide transcriptional regulatory dynamics of Halobacterium salinarum, an extremophile that thrives in extremely high salinity. This "regulatory influence" network was derived through an iterative process of directed experimentation followed by statistical modeling and data integration. I will briefly review this first draft model, the methods behind its development, and its current limitations. Then, I will present our recent ongoing efforts to decipher the mechanics which underly the predictions, through modeling of high-resolution tiling array (ChIP-chip and mRNA hybridization) data.
  • R Bonneau, MT Facciotti, DJ Reiss, AK Schmid, M Pan, A Kaur, V Thorsson, P Shannon, MH Johnson, JC Bare, W Longabaugh, M Vuthoori, K Whitehead, A Madar, L Suzuki, T Mori, DE Chang, J Diruggiero, CH Johnson, L Hood, NS Baliga, "A predictive model for transcriptional control of physiology in a free living cell." Cell, 131, #7 (2007) 1354-65. [offcampus]
(and references therein, including Inferelator and cMonkey algorithms)

04/21: Inferring Biological Pathways through Constrained Searching of Molecular Interaction Graphs -- Imran Rashid

   Abstract:   Recent advances in biology have provided a great deal of information on single genes and on the interactions between pairs of genes. Yet true biological pathways involve a large number of genes working in concert. Even when biologists know that two genes are indirectly related, in general they cannot discern the underlying pathway, without a great deal of additional experimentation. Here, we propose a method to discover novel biological pathways by integrating previously existing knowledge of gene interactions. We model interacting genes as a graph, and use direct graph search methods to discover pathways. Finally, we propose novel biologically sensible (yet computationally simple) pathway constraints to improve accuracy.

04/28: Systematic discovery of vertebrate regulatory elements -- Adrienne Wang

   Abstract:   A few groups have constructed whole-genome catalogs of vertebrate regulatory elements using comparative genomic approaches. However, determining truly orthologous promoter sequences, which is a prerequisite for identifying conserved regulatory elements, remains a very challenging problem. Prakash and Tompa observed that the regions upstream of annotated transcription start sites are often not orthologous. Starting from such non-orthologous sequences could very possibly affect the downstream analyses. Studies in the past have applied various filters to ensure orthology, resulting in a very limited set of genes and species to start with. Our goal is to build a catalog of regulatory elements for most human genes. For each human gene, we align its promoter region and syntenic vertebrate regions from both Ensembl and the UCSC Genome Browser. To avoid the adverse effect described above, we apply StatSigMA, an assessment tool for multiple sequence alignments, as a filter to retain only the genes where there is compelling evidence that the promoter regions are truly orthologous. Well conserved motifs extracted from the alignments are strong candidates for regulatory elements.

05/05: Finding non-coding RNAs through genome-scale clustering -- Elizabeth Tseng

   Abstract:   Non-coding RNAs (ncRNAs) are transcripts that do not code for proteins. Recent findings have shown that RNA-mediated regulatory mechanisms influence a substantial portion of typical microbial genomes. We present an efficient method for finding potential ncRNAs in bacteria by clustering genomic sequences based on homology inferred from both primary sequence and secondary structure. We evaluate our approach using a set of Firmicutes sequences, and the results show promise for discovering new ncRNAs.

05/12: TBA -- Harlan Robins, FHCRC

05/19: String Matching and Next Generation Sequencing -- Robert Gentleman, FHCRC

   Abstract:   The advent of several technologies (454, BASE, Solexa) has made many new biological experiments possible and changed the way that some experiments will be carried out. These technologies produce tens of thousands to tens of millions of short reads (250 nt or less). The computational problems that arise are largely related to matching of these many query sequences to somewhat longer target sequences. There is great interest in tools for quality assessment and for performing imperfect matching. I will discuss some of the basic problems, and some solutions that are available through the Bioconductor project.

Familiarity with some string processing methods like the Aho-Corasick algorithm ( ) or suffix trees ( ) might be helpful, but not essential, background.

05/26: Holiday

06/02:  Join us all afternoon in room CSE 403, especially for the keynote at 4:00:
Dr. Joseph Felsenstein, 2008 Darwin-Wallace Medal Winner, ``Developing and distributing a phylogeny package: tales of the PHYLIP''
-- Special Event:
CMB Symposium

   Abstract:   I will describe how the PHYLIP phylogeny inference package developed and has been distributed. In its 27 years of continuous development, it has grown and improved greatly and its developer is wiser, and perhaps sadder. I will explain some of the decisions made, assess whether they were correct ones, and try to give some sense of the reactions it has gotten, the triumphs, the tragedies, and the dilemmas that it faces in the future.

 Other  Seminars Past quarters of CSE 590C
COMBI & Genome Sciences Seminars
Applied Math Department Mathematical Biology Journal Club
Biostatistics Seminars
Microbiology Department Seminars
Zoology 525, Mathematical Biology Seminar Series

 Resources Molecular Biology for Computer Scientists, a primer by Lawrence Hunter (46 pages)
A Quick Introduction to Elements of Biology, a primer by Alvis Brazma et al.
S-Star Bioinformatics Online Course Schedule, a collection of video primers
A very comprehensive FAQ at, including annotated references to online tutorials and lectures.
CSE 527: Computational Biology
CSE 590TV: Computational Biology (Professional Masters Program)
Genome 540/541: Introduction to Computational Molecular Biology: Genome and Protein Sequence Analysis

CSE's Computational Molecular Biology research group
Interdisciplinary Ph.D. program in Computational Molecular Biology

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