Probabilistic clustering of sequences: Inferring new bacterial regulons by comparative genomics

DOI10.1073/PNAS.112690399MaRDI QIDQ4547713zbMATH OpenOpenAlexWikidataFDO

Authors Erik Van Nimwegen, Mihaela Zavolan, N. Rajewsky, Eric D. Siggia

Publication date 11 September 2002

Published in Proceedings of the National Academy of Sciences (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/physics/0206045, https://europepmc.org/articles/pmc124229, http://www.pnas.org/content/vol99/issue11/#APPLIED_MATHEMATICS

Mathematics Subject Classification ID

Biochemistry, molecular biology (92C40) Protein sequences, DNA sequences (92D20) Computational methods for problems pertaining to biology (92-08)

Abstract: Genome wide comparisons between enteric bacteria yield large sets of conserved putative regulatory sites on a gene by gene basis that need to be clustered into regulons. Using the assumption that regulatory sites can be represented as samples from weight matrices we derive a unique probability distribution for assignments of sites into clusters. Our algorithm, 'PROCSE' (probabilistic clustering of sequences), uses Monte-Carlo sampling of this distribution to partition and align thousands of short DNA sequences into clusters. The algorithm internally determines the number of clusters from the data, and assigns significance to the resulting clusters. We place theoretical limits on the ability of any algorithm to correctly cluster sequences drawn from weight matrices (WMs) when these WMs are unknown. Our analysis suggests that the set of all putative sites for a single genome (e.g. E. coli) is largely inadequate for clustering. When sites from different genomes are combined and all the homologous sites from the various species are used as a block, clustering becomes feasible. We predict 50-100 new regulons as well as many new members of existing regulons, potentially doubling the number of known regulatory sites in E. coli.

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Cited in

(5)

• Subset Clustering of Binary Sequences, with an Application to Genomic Abnormality Data
• Whole-genome prokaryotic clustering based on gene lengths
• Genome-wide analysis of bacterial promoter regions
• PathOGiST: A Novel Method for Clustering Pathogen Isolates by Combining Multiple Genotyping Signals
• Information content based model for the topological properties of the gene regulatory network of \textit{Escherichia coli}

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