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Pfam: A Comprehensive Database of Protein Domain Families Based on Seed Alignments

At publication, the database lists 22 studies linking pesticides to reproductive health effects. These include decreased fertility in both males and females, antiandrogenic (demasculinizing) effects, increased rates of miscarriage, altered sex ratios and altered maturity. A 2006 study published in the journal Epidemiology has found inverse associations between pesticides and male testosterone levels. The study found that high levels of the urinary metabolites of chlorpyrifos (TCPY) and carbaryl and naphthalene (1N) correlate directly with low levels of testosterone in male subjects. 16 A number of epidemiological studies and animal laboratory experiments that show strong associations or linkages between. | PROTEINS Structure Function and Genetics 28 405-420 1997 Pfam A Comprehensive Database of Protein Domain Families Based on Seed Alignments Erik L.L. Sonnhammer 1 Sean R. Eddy 2 and Richard Durbin1 1 Sanger Centre Wellcome Trust Genome Campus Hinxton Cambridge CB10 ISA United Kingdom 2 Department of Genetics Washington University School of Medicine St. Louis Missouri ABSTRACT Databases of multiple sequence alignments are a valuable aid to protein sequence classi cation and analysis. One of the main challenges when constructing such a database is to simultaneously satisfy the conflicting demands of completeness on the one hand and quality of alignment and domain definitions on the other. The latter properties are best dealt with by manual approaches whereas completeness in practice is only amenable to automatic methods. Herein we present a database based on hidden Markov model profiles HMMs which combines high quality and completeness. Our database Pfam consists of parts A and B. Pfam-A is curated and contains well-characterized protein domain families with high quality alignments which are maintained by using manually checked seed alignments and HMMs to find and align all members. Pfam-B contains sequence families that were generated automatically by applying the Domainer algorithm to cluster and align the remaining protein sequences after removal of Pfam-A domains. By using Pfam a large number of previously unannotated proteins from the Caenorhabditis elegans genome project were classified. We have also identified many novel family memberships in known proteins including new kazal Fibronectin type III and response regulator receiver domains. Pfam-A families have permanent accession numbers and form a library of HMMs available for searching and automatic annotation of new protein sequences. Proteins 28 405-420 1997. r 1997 Wiley-Liss Inc. Key words classification clustering protein domains genome annotation hidden Markov model Caenorhabdi-tis elegans INTRODUCTION .