Evolutionary analysis of enzymes using Chisel

Motivation: Availability of large volumes of genomic and enzymatic data for taxonomically and phenotypically diverse organisms allows for exploration of the adaptive mechanisms that led to diversification of enzymatic functions. We present Chisel, a computational framework and a pipeline for an automated, high-resolution analysis of evolutionary variations of enzymes. Chisel allows automatic as well as interactive identification, and characterization of enzymatic sequences. Such knowledge can be utilized for comparative genomics, microbial diagnostics, metabolic engineering, drug design and analysis of metagenomes. Results: Chisel is a comprehensive resource that contains 8575 clusters and subsequent computational models specific for 939 distinct enzymatic functions and, when data is sufficient, their taxonomic variations. Application of Chisel to identification of enzymatic sequences in newly sequenced genomes, analysis of organism-specific metabolic networks, binning of metagenomes and other biological problems are presented. We also provide a thorough analysis of Chisel performance with other similar resources and manual annotations on Shewanella oneidensis MR1 genome. Availability: Chisel is available for interactive use at http://compbio.mcs.anl.gov/CHISEL. The website also provides a user manual, clusters and function-specific computational models. Contact: arodri7@mcs.anl.gov or maltsev@mcs.anl.gov Supplementary information: Additional data can be found at http://compbio.mcs.anl.gov/CHISEL/htmls/refs.html.