{"doi":"10.1006/jmbi.2000.4315","title":"Predicting transmembrane protein topology with a hidden markov model: application to complete genomes11Edited by F. Cohen","abstract":"We describe and validate a new membrane protein topology prediction method, TMHMM, based on a hidden Markov model. We present a detailed analysis of TMHMM's performance, and show that it correctly predicts 97-98 % of the transmembrane helices. Additionally, TMHMM can discriminate between soluble and membrane proteins with both specificity and sensitivity better than 99 %, although the accuracy drops when signal peptides are present. This high degree of accuracy allowed us to predict reliably integral membrane proteins in a large collection of genomes. Based on these predictions, we estimate that 20-30 % of all genes in most genomes encode membrane proteins, which is in agreement with previous estimates. We further discovered that proteins with N(in)-C(in) topologies are strongly preferred in all examined organisms, except Caenorhabditis elegans, where the large number of 7TM receptors increases the counts for N(out)-C(in) topologies. We discuss the possible relevance of this finding for our understanding of membrane protein assembly mechanisms. A TMHMM prediction service is available at http://www.cbs.dtu.dk/services/TMHMM/.","journal":"Journal of Molecular Biology","year":2001,"id":5538,"datarank":20.589339272054573,"base_score":9.46792399660393,"endowment":9.46792399660393,"self_citation_contribution":1.4201885994905898,"citation_network_contribution":19.169150672563983,"self_endowment_contribution":1.4201885994905898,"citer_contribution":19.169150672563983,"corpus_percentile":96.9,"corpus_rank":616,"citation_count":12937,"citer_count":189,"citers_with_citation_signal":189,"citers_with_endowment":189,"datacite_reuse_total":0,"is_dataset":false,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2001-01-01","authors":[{"id":54424,"name":"Björn Larsson","orcid":null,"position":1,"is_corresponding":false},{"id":54425,"name":"Gunnar von Heijne","orcid":"0000-0002-4490-8569","position":2,"is_corresponding":false},{"id":54426,"name":"Erik L.L Sonnhammer","orcid":null,"position":3,"is_corresponding":false},{"id":54427,"name":"B. Larsson","orcid":null,"position":4,"is_corresponding":false},{"id":54428,"name":"Erik L. L. Sonnhammer","orcid":"0000-0002-9015-5588","position":5,"is_corresponding":false},{"id":54423,"name":"Anders Krogh","orcid":"0000-0002-5147-6282","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}