Call for Papers and Posters

Protein-DNA Interactions: Integrating Structure, Sequence, and Function

Session at the Pacific Symposium on Biocomputing 2007

 

Transcription of genes is in large measure regulated by proteins that bind to DNA. These include the basal transcription apparatus recognizing the core promoter and its associated general transcription factors, as well as a host of other more specialized transcription factors that combinatorially regulate the transcription of specific subsets of genes through DNA-binding events. These also include nucleosome-forming histones that regulate the structure of chromatin fibers, as well as factors like DNA methylases that mark the genome epigenetically, in some cases completely silencing gene expression. The manner in which cells regulate expression of genes through protein-DNA interactions has largely been studied either through structural experimental approaches (for example, structure determination of the polymerase holoenzyme, or of a leucine zipper co-crystallized with its DNA substrate) or through computational approaches based on sequence data (for example, de novo motif finding algorithms, or phylogenetic footprinting) or functional expression data (for example, using gene expression data to infer genetic regulatory networks). However, structural information about proteins and about DNA (e.g., chromatin) can clearly be useful in accurately interpreting patterns in the expression data of co-regulated genes and in finding regulatory motifs in sequences that are subtler or weaker than can be found with current motif-finding algorithms.

Recent technological advances enable us to collect many different types of data at a genome-wide and proteome-wide scale, including: DNA sequence from various kinds of genomes, gene expression data, protein-protein and protein-ligand interactions, and protein-DNA binding data. In addition, efforts in structural biology are yielding structural data on proteins, protein complexes, and protein-ligand interactions. These data provide us, for the first time, with the opportunity to integrate data from functional studies with structural data, in order to understand how the biophysical aspects of protein-DNA interactions affect their functions. Indeed, much recent work has been devoted to analyzing these data for various focused aspects of this purpose, such as either the regulatory aspects of protein-DNA interactions or the structural aspects of protein-DNA recognition. However, very few studies have integrated these various types of data in order to bridge this divide between structure, sequence, and function together.

This session focuses on novel methods and studies that employ multiple perspectives--specifically a combination of structure, sequence, and function--in their analysis. The output of such analyses will produce results and findings based on more than one type of data, leading to several key advantages. First, structural data alone often do not permit the inference of biological function. Second, functional studies typically do not connect function to structure. Indeed, there has been only a small amount of work that addresses how to take advantage of these currently separate areas of research on protein-DNA interactions. Third, most experimental genomic data sets often contain errors arising from imperfections in the applied technology. Combining these different types of data may allow us to combine the advantages of different perspectives, as well as reduce systematic noise, to better identify essential biological associations, and ultimately to model and predict these interactions. Finally, structural data, sequence data, and functional data are quite different from one another and thus typically have been the subject of study of distinct groups of investigators. Thus, methods and studies combining these different types of analysis and data for the discovery process will likely result in the formation of new collaborations for the purpose of deeper understanding of protein-DNA interactions and their impact on gene regulation and other cellular processes.

Session Focus:

The session will focus on methods and studies that bridge structure, sequence, and function to infer previously undiscovered associations between these different aspects of protein-DNA interactions. For example, can available experimental data on genome-wide protein-DNA interactions allow one to infer structure-related features of these interactions; or vice versa: how does knowledge of structure allow one to find sequence motifs with greater sensitivity and specificity? As another example, do certain types of domains of DNA-binding proteins confer particular biophysical properties, either in terms of kinetics or ligand specificity, that would better explain their use by the cell in transcriptional regulation of certain classes of genes? As yet another example, has there been an evolutionary selection for the usage of certain structural classes of DNA binding proteins in particular types of biological pathways?

There will be a preference towards papers that combine the following types of data: protein-DNA interaction data (e.g., from ChIP-chip, protein binding microarray, or in vitro selection), protein or DNA 3D structure data (or protein-DNA 3D structure data), phylogenetic conservation from comparative genomic sequencing efforts, and gene expression data. Information from functional annotation databases, protein-DNA interaction databases, literature mining, or data regarding protein-protein interactions will also be considered if it is applied to the specific problem of the session: as just one example, perhaps a protein-protein complex explains a particular aspect of transcriptional regulation because it explains how a transcription factor can affect the expression of a gene without binding directly to DNA, but via a DNA-binding partner.

Individuals who cannot submit to this session but are willing to help referee submissions are kindly requested to contact one of the session co-chairs.

General Information on PSB 2007:

The Pacific Symposium on Biocomputing (PSB) 2007 is an international, multidisciplinary conference for the presentation and discussion of current research in the theory and application of computational methods in problems of biological significance. Papers and presentations are rigorously peer reviewed and are published in an archival proceedings volume. PSB 2007 will be held January 3-7, 2007 at the Grand Wailea in Wailea, Maui. Tutorials will be offered prior to the start of the conference.

PSB 2007 will bring together top researchers from the US, the Asian Pacific nations, and around the world to exchange research results and address open issues in all aspects of computational biology. PSB is a forum for the presentation of work in databases, algorithms, interfaces, visualization, modeling, and other computational methods, as applied to biological problems, with emphasis on applications in data-rich areas of molecular biology.

The PSB has been designed to be responsive to the need for critical mass in sub-disciplines within biocomputing. For that reason, it is the only meeting whose sessions are defined dynamically each year in response to specific proposals. PSB sessions are organized by leaders in the emerging areas and targeted to provide a forum for publication and discussion of research in biocomputing's "hot topics." In this way, PSB provides an early forum for serious examination of emerging methods and approaches in this rapidly changing field. More information on the conference can be obtained from the conference web page: http://psb.stanford.edu/.

General Information on Papers, Abstracts, and Demonstrations:

The scientific core of the conference consists of rigorously peer-reviewed full-length papers reporting on original work. Accepted papers will be published in a hard-bound archival proceedings volume (which is fully indexed in Medline), and the best of these will be presented orally to the entire conference. Researchers wishing to present their research without official publication are encouraged to submit a one page abstract, and present their work in a poster session.

Paper Formatting and Submission:

All papers must be submitted to psb-submit @ helix.stanford.edu in electronic format. The only acceptable file formats are Adobe Acrobat (*.pdf) and postscript (*.ps). Attached files should be named with the last name of the first author (e.g., altman.pdf or altman.ps). Hardcopy submissions or unprocessed TeX or LaTeX files will be rejected without review.

Each paper must be accompanied by a cover letter. The cover letter must state the following:

  • The email address of the corresponding author
  • The specific PSB session that should review the paper or abstract
  • The submitted paper contains original, unpublished results, and is not currently under consideration elsewhere
  • All co-authors concur with the contents of the paper

Submitted papers are limited to twelve (12) pages in the official PSB publication format. Please format your paper according to these instructions, which can be found at http://psb.stanford.edu/psb-online/psb-submit/. If figures cannot be easily resized and placed precisely in the text, then it should be clear that with appropriate modifications, the total manuscript length would be within the page limit.

Important Dates:

  • Paper submission deadline: July 17, 2006
  • Notification of paper acceptance: September 6, 2006
  • Final paper deadline: September 25, 2006
  • Poster abstract deadline: November 10, 2006
  • Meeting: January 3-7, 2007

Session Co-chairs: