Computational systems bioinformatics. Computational Systems Bioinformatics Conference最新文献

In molecular biology research, looking for information on a particular entity such as a gene or a protein may lead to thousands of articles, making it impossible for a researcher to individually read these articles and even just their abstracts. Thus, there is a need to curate the literature to get various nuggets of knowledge, such as an interaction between two proteins, and store them in a database. However the body of existing biomedical articles is growing at a very fast rate, making it impossible to curate them manually. An alternative approach of using computers for automatic extraction has problem with accuracy. We propose to leverage the advantages of both techniques, extracting binary relationships between biological entities automatically from the biomedical literature and providing a platform that allows community collaboration in the annotation of the extracted relationships. Thus, the community of researchers that writes and reads the biomedical texts can use the server for searching our database of extracted facts, and as an easy-to-use web platform to annotate facts relevant to them. We presented a preliminary prototype as a proof of concept earlier(1). This paper presents the working implementation available for download at http://www.cbioc.org as a browser-plug in for both Internet Explorer and FireFox. This current version has been available since June of 2006, and has over 160 registered users from around the world. Aside from its use as an annotation tool, data from CBioC has also been used in computational methods with encouraging results.

Peptide sequencing by tandem mass spectrometry is a very important, interesting, yet challenging problem in proteomics. This problem is extensively investigated by researchers recently, and the peptide sequencing results are becoming more and more accurate. However, many of these algorithms are using computational models based on some unverified assumptions. We believe that the investigation of the validity of these assumptions and related problems will lead to improvements in current algorithms. In this paper, we have first investigated peptide sequencing without preprocessing the spectrum, and we have shown that by introducing preprocessing on spectrum, peptide sequencing can be faster, easier and more accurate. We have then investigated one very important problem, the anti-symmetric problem in the peptide sequencing problem, and we have proved by experiments that model that simply ignore anti-symmetric of model that remove all anti-symmetric instances are too simple for peptide sequencing problem. We have proposed a new model for anti-symmetric problem in more realistic way. We have also proposed a novel algorithm which incorporate preprocessing and new model for anti-symmetric issue, and experiments show that this algorithm has better performance on datasets examined.

We present a method for detecting and comparing cavities on protein surfaces that is useful for protein binding site recognition. The method is based on a representation of the protein structures by a collection of spin-images and their associated spin-image profiles. Results of the cavity detection procedure are presented for a large set of non-redundant proteins and compared with SURFNET-ConSurf. Our comparison method is used to find a surface region in one cavity of a protein that is geometrically similar to a surface region in the cavity of another protein. Such a finding would be an indication that the two regions likely bind to the same ligand. Our overall approach for cavity detection and comparison is benchmarked on several pairs of known complexes, obtaining a good coverage of the atoms of the binding sites.

Statistical relations between genome-wide mRNA transcript levels have been successfully used to infer regulatory relations among the genes, however the most successful methods have relied on additional data and focused on small sub-networks of genes. Along these lines, we recently demonstrated a model for simultaneously incorporating micro-array expression data with whole genome genotype marker data to identify causal pairwise relationships among genes. In this paper we extend this methodology to the principled construction of networks describing local regulatory modules. Our method is a two-step process: starting with a seed gene of interest, a Markov Blanket over genotype and gene expression observations is inferred according to differential entropy estimation; a Bayes Net is then constructed from the resulting variables with important biological constraints yielding causally correct relationships. We tested our method by simulating a regulatory network within the background of of a real data set. We found that 45% of the genes in a regulatory module can be identified and the relations among the genes can be recovered with moderately high accuracy (> 70%). Since sample size is a practical and economic limitation, we considered the impact of increasing the number of samples and found that recovery of true gene-gene relationships only doubled with ten times the number of samples, suggesting that useful networks can be achieved with current experimental designs, but that significant improvements are not expected without major increases in the number of samples. When we applied this method to an actual data set of 111 back-crossed mice we were able to recover local gene regulatory networks supported by the biological literature.