{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T12:24:46Z","timestamp":1763468686088,"version":"3.37.3"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"22-23","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM103773","R01GM116960","R35GM118166","R01GM126299"],"award-info":[{"award-number":["R01GM103773","R01GM116960","R35GM118166","R01GM126299"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>The binding of T-cell receptors (TCRs) to their target peptide MHC (pMHC) ligands initializes the cell-mediated immune response. In autoimmune diseases such as multiple sclerosis, the TCR erroneously recognizes self-peptides as foreign and activates an immune response against healthy cells. Such responses can be triggered by cross-recognition of the autoreactive TCR with foreign peptides. Hence, it would be desirable to identify such foreign-antigen triggers to provide a mechanistic understanding of autoimmune diseases. However, the large sequence space of foreign antigens presents an obstacle in the identification of cross-reactive peptides.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Here, we present an in silico modeling and scoring method which exploits the structural properties of TCR-pMHC complexes to predict the binding of cross-reactive peptides. We analyzed three mouse TCRs and one human TCR isolated from a patient with multiple sclerosis. Cross-reactive peptides for these TCRs were previously identified via yeast display coupled with deep sequencing, providing a robust dataset for evaluating our method. Modeling query peptides in their associated TCR-pMHC crystal structures, our method accurately selected the top binding peptides from sets containing more than a hundred thousand unique peptides.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Analyses were performed using custom Python and R scripts available at https:\/\/github.com\/weng-lab\/antigen-predict.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaa1050","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T05:04:36Z","timestamp":1607490276000},"page":"5377-5385","source":"Crossref","is-referenced-by-count":18,"title":["High-throughput modeling and scoring of TCR-pMHC complexes to predict cross-reactive peptides"],"prefix":"10.1093","volume":"36","author":[{"given":"Tyler","family":"Borrman","sequence":"first","affiliation":[{"name":"Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School , Worcester, MA 01605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian G","family":"Pierce","sequence":"additional","affiliation":[{"name":"University of Maryland Institute for Bioscience and Biotechnology Research , Rockville, MD 20850, USA"},{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland , College Park, MD 20742, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thom","family":"Vreven","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School , Worcester, MA 01605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian M","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, IN 46556, USA"},{"name":"Harper Cancer Research Institute, University of Notre Dame , Notre Dame, IN 46556, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3032-7966","authenticated-orcid":false,"given":"Zhiping","family":"Weng","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School , Worcester, MA 01605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,12,23]]},"reference":[{"key":"2023062708405491200_btaa1050-B1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/ni.3310","article-title":"Structural interplay between germline interactions and adaptive recognition determines the bandwidth of TCR-peptide-MHC cross-reactivity","volume":"17","author":"Adams","year":"2016","journal-title":"Nat. Immunol"},{"key":"2023062708405491200_btaa1050-B2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/bioinformatics\/btv639","article-title":"Gapped sequence alignment using artificial neural networks: application to the MHC class i system","volume":"32","author":"Andreatta","year":"2016","journal-title":"Bioinformatics"},{"key":"2023062708405491200_btaa1050-B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2017.00935","article-title":"Peptide and peptide-dependent motions in MHC proteins: immunological implications and biophysical underpinnings","volume":"8","author":"Ayres","year":"2017","journal-title":"Front. Immunol"},{"key":"2023062708405491200_btaa1050-B4","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/nbt.4303","article-title":"T cell receptor fingerprinting enables in-depth characterization of the interactions governing recognition of peptide\u2013MHC complexes","volume":"36","author":"Bentzen","year":"2018","journal-title":"Nat. Biotechnol"},{"key":"2023062708405491200_btaa1050-B5","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1038\/nbt.3662","article-title":"Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes","volume":"34","author":"Bentzen","year":"2016","journal-title":"Nat. Biotechnol"},{"key":"2023062708405491200_btaa1050-B6","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1110\/ps.03373104","article-title":"Analysis and prediction of affinity of TAP binding peptides using cascade SVM","volume":"13","author":"Bhasin","year":"2004","journal-title":"Protein Sci"},{"key":"2023062708405491200_btaa1050-B7","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.cell.2014.03.047","article-title":"Deconstructing the peptide-MHC specificity of T cell recognition","volume":"157","author":"Birnbaum","year":"2014","journal-title":"Cell"},{"key":"2023062708405491200_btaa1050-B8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2017.01566","article-title":"An analysis of natural T cell responses to predicted tumor neoepitopes","volume":"8","author":"Bjerregaard","year":"2017","journal-title":"Front. Immunol"},{"key":"2023062708405491200_btaa1050-B9","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.4049\/jimmunol.1003150","article-title":"Conformational melding permits a conserved binding geometry in TCR recognition of foreign and self molecular mimics","volume":"186","author":"Borbulevych","year":"2011","journal-title":"J. Immunol. (Baltimore, MD: 1950)"},{"key":"2023062708405491200_btaa1050-B10","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.immuni.2009.11.003","article-title":"T cell receptor cross-reactivity directed by antigen-dependent tuning of peptide-MHC molecular flexibility","volume":"31","author":"Borbulevych","year":"2009","journal-title":"Immunity"},{"key":"2023062708405491200_btaa1050-B11","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/prot.25260","article-title":"ATLAS: a database linking binding affinities with structures for wild-type and mutant TCR-pMHC complexes","volume":"85","author":"Borrman","year":"2017","journal-title":"Proteins Struct. Funct. Bioinf"},{"key":"2023062708405491200_btaa1050-B12","doi-asserted-by":"crossref","first-page":"e1003266","DOI":"10.1371\/journal.pcbi.1003266","article-title":"Properties of MHC class I presented peptides that enhance immunogenicity","volume":"9","author":"Calis","year":"2013","journal-title":"PLoS Comput. Biol"},{"key":"2023062708405491200_btaa1050-B13","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jim.2008.09.016","article-title":"Engineering higher affinity T cell receptors using a T cell display system","volume":"339","author":"Chervin","year":"2008","journal-title":"J. Immunol. Methods"},{"key":"2023062708405491200_btaa1050-B14","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jmb.2006.08.045","article-title":"T cell receptor recognition via cooperative conformational plasticity","volume":"363","author":"Gagnon","year":"2006","journal-title":"J. Mol. Biol"},{"key":"2023062708405491200_btaa1050-B15","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.cell.2017.11.043","article-title":"Antigen identification for orphan T cell receptors expressed on tumor-infiltrating lymphocytes","volume":"172","author":"Gee","year":"2018","journal-title":"Cell"},{"key":"2023062708405491200_btaa1050-B16","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jaut.2013.06.004","article-title":"Promotion and prevention of autoimmune disease by CD8+ T cells","volume":"45","author":"Gravano","year":"2013","journal-title":"J. Autoimmun"},{"key":"2023062708405491200_btaa1050-B17","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/ni1187","article-title":"Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor","volume":"6","author":"Hahn","year":"2005","journal-title":"Nat. Immunol"},{"key":"2023062708405491200_btaa1050-B18","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.4049\/jimmunol.1302953","article-title":"TCR scanning of peptide\/MHC through complementary matching of receptor and ligand molecular flexibility","volume":"192","author":"Hawse","year":"2014","journal-title":"J. Immunol"},{"key":"2023062708405491200_btaa1050-B19","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.ymthe.2018.12.010","article-title":"Improving T cell receptor on-target specificity via structure-guided design","volume":"27","author":"Hellman","year":"2019","journal-title":"Mol. Therapy"},{"key":"2023062708405491200_btaa1050-B20","doi-asserted-by":"crossref","first-page":"10915","DOI":"10.1073\/pnas.89.22.10915","article-title":"Amino acid substitution matrices from protein blocks","volume":"89","author":"Henikoff","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023062708405491200_btaa1050-B21","doi-asserted-by":"crossref","first-page":"5387","DOI":"10.1073\/pnas.080078297","article-title":"In vitro evolution of a T cell receptor with high affinity for peptide\/MHC","volume":"97","author":"Holler","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023062708405491200_btaa1050-B22","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.4049\/jimmunol.1700893","article-title":"NetMHCpan-4.0: improved peptide\u2013MHC class I interaction predictions integrating eluted ligand and peptide binding affinity data","volume":"199","author":"Jurtz","year":"2017","journal-title":"J. Immunol"},{"key":"2023062708405491200_btaa1050-B23","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.cell.2019.07.009","article-title":"T-Scan: a genome-wide method for the systematic discovery of T cell epitopes","volume":"178","author":"Kula","year":"2019","journal-title":"Cell"},{"key":"2023062708405491200_btaa1050-B24","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.molimm.2017.12.019","article-title":"Identification of the cognate peptide-MHC target of T cell receptors using molecular modeling and force field scoring","volume":"94","author":"Lanzarotti","year":"2018","journal-title":"Mol. Immunol"},{"key":"2023062708405491200_btaa1050-B25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2019.02080","article-title":"T-cell receptor cognate target prediction based on paired \u03b1 and \u03b2 chain sequence and structural CDR loop similarities","volume":"10","author":"Lanzarotti","year":"2019","journal-title":"Front. Immunol"},{"first-page":"343","year":"2008","author":"Leaver-Fay","key":"2023062708405491200_btaa1050-B26"},{"key":"2023062708405491200_btaa1050-B27","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/B978-0-12-381270-4.00019-6","article-title":"ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules","volume":"487","author":"Leaver-Fay","year":"2011","journal-title":"Methods Enzymol"},{"key":"2023062708405491200_btaa1050-B28","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nbt1070","article-title":"Directed evolution of human T-cell receptors with picomolar affinities by phage display","volume":"23","author":"Li","year":"2005","journal-title":"Nat. Biotechnol"},{"key":"2023062708405491200_btaa1050-B29","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1182\/blood-2013-03-490565","article-title":"Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma","volume":"122","author":"Linette","year":"2013","journal-title":"Blood"},{"key":"2023062708405491200_btaa1050-B30","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.immuni.2009.09.025","article-title":"T cell allorecognition via molecular mimicry","volume":"31","author":"Macdonald","year":"2009","journal-title":"Immunity"},{"key":"2023062708405491200_btaa1050-B31","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S0167-5699(98)01299-7","article-title":"A very high level of crossreactivity is an essential feature of the T-cell receptor","volume":"19","author":"Mason","year":"1998","journal-title":"Immunol. Today"},{"key":"2023062708405491200_btaa1050-B32","first-page":"81","article-title":"Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity","volume":"22","author":"Maynard","year":"2005","journal-title":"Immunity"},{"key":"2023062708405491200_btaa1050-B33","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1097\/CJI.0b013e3182829903","article-title":"Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy","volume":"36","author":"Morgan","year":"2013","journal-title":"J. Immunother"},{"key":"2023062708405491200_btaa1050-B34","doi-asserted-by":"crossref","first-page":"5823","DOI":"10.4049\/jimmunol.1100197","article-title":"Structural basis of specificity and cross-reactivity in T cell receptors specific for cytochrome c-I-E(k)","volume":"186","author":"Newell","year":"2011","journal-title":"J. Immunol"},{"key":"2023062708405491200_btaa1050-B35","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s00251-005-0781-7","article-title":"The role of the proteasome in generating cytotoxic T-cell epitopes: insights obtained from improved predictions of proteasomal cleavage","volume":"57","author":"Nielsen","year":"2005","journal-title":"Immunogenetics"},{"key":"2023062708405491200_btaa1050-B36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0059004","article-title":"A pareto-optimal refinement method for protein design scaffolds","volume":"8","author":"Nivon","year":"2013","journal-title":"PLoS One"},{"key":"2023062708405491200_btaa1050-B37","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.cels.2018.05.014","article-title":"MHCflurry: open-source class I MHC binding affinity prediction","volume":"7","author":"O'Donnell","year":"2018","journal-title":"Cell Syst"},{"key":"2023062708405491200_btaa1050-B38","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/nbt.3147","article-title":"Identification of human T-cell receptors with optimal affinity to cancer antigens using antigen-negative humanized mice","volume":"33","author":"Obenaus","year":"2015","journal-title":"Nat. Biotechnol"},{"key":"2023062708405491200_btaa1050-B39","doi-asserted-by":"crossref","first-page":"827","DOI":"10.3389\/fimmu.2019.00827","article-title":"Quantitative prediction of the landscape of T cell epitope immunogenicity in sequence space","volume":"10","author":"Ogishi","year":"2019","journal-title":"Front. Immunol"},{"key":"2023062708405491200_btaa1050-B40","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/pro.2181","article-title":"A flexible docking approach for prediction of T cell receptor-peptide-MHC complexes","volume":"22","author":"Pierce","year":"2013","journal-title":"Protein Sci"},{"key":"2023062708405491200_btaa1050-B41","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/ni891","article-title":"CDR3 loop flexibility contributes to the degeneracy of TCR recognition","volume":"4","author":"Reiser","year":"2003","journal-title":"Nat. Immunol"},{"key":"2023062708405491200_btaa1050-B42","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S1074-7613(02)00288-1","article-title":"A T cell receptor CDR3\u03b2 loop undergoes conformational changes of unprecedented magnitude upon binding to a peptide\/MHC class I complex","volume":"16","author":"Reiser","year":"2002","journal-title":"Immunity"},{"key":"2023062708405491200_btaa1050-B43","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.semcdb.2017.10.017","article-title":"The intersection of affinity and specificity in the development and optimization of T cell receptor based therapeutics","volume":"84","author":"Riley","year":"2018","journal-title":"Semin. Cell Dev. Biol"},{"key":"2023062708405491200_btaa1050-B44","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/s41589-018-0130-4","article-title":"T cell receptor cross-reactivity expanded by dramatic peptide\u2013MHC adaptability","volume":"14","author":"Riley","year":"2018","journal-title":"Nat. Chem. Biol"},{"key":"2023062708405491200_btaa1050-B45","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.3389\/fimmu.2019.02047","article-title":"Structure based prediction of neoantigen immunogenicity","volume":"10","author":"Riley","year":"2019","journal-title":"Front. Immunol"},{"key":"2023062708405491200_btaa1050-B46","doi-asserted-by":"crossref","first-page":"e0206654","DOI":"10.1371\/journal.pone.0206654","article-title":"Predicting CD4 T-cell epitopes based on antigen cleavage, MHCII presentation, and TCR recognition","volume":"13","author":"Schneidman-Duhovny","year":"2018","journal-title":"PLoS One"},{"key":"2023062708405491200_btaa1050-B47","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jmb.2011.10.006","article-title":"Disparate degrees of hypervariable loop flexibility control T-cell receptor cross-reactivity, specificity, and binding mechanism","volume":"414","author":"Scott","year":"2011","journal-title":"J. Mol. Biol"},{"key":"2023062708405491200_btaa1050-B48","first-page":"669","article-title":"Why must T cells be cross-reactive?","volume":"12","author":"Sewell","year":"2012","journal-title":"Nat. Publish. Group"},{"key":"2023062708405491200_btaa1050-B49","doi-asserted-by":"crossref","first-page":"3940","DOI":"10.1093\/bioinformatics\/bti623","article-title":"ROCR: visualizing classifier performance in R","volume":"21","author":"Sing","year":"2005","journal-title":"Bioinformatics"},{"key":"2023062708405491200_btaa1050-B50","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.4049\/jimmunol.1700744","article-title":"Emerging concepts in TCR specificity: rationalizing and (Maybe) predicting outcomes","volume":"199","author":"Singh","year":"2017","journal-title":"J. Immunol"},{"key":"2023062708405491200_btaa1050-B51","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1158\/2326-6066.CIR-19-0155","article-title":"Machine-learning prediction of tumor antigen immunogenicity in the selection of therapeutic epitopes","volume":"7","author":"Smith","year":"2019","journal-title":"Cancer Immunol. Res"},{"key":"2023062708405491200_btaa1050-B52","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1186\/1471-2105-12-446","article-title":"POPISK: t -cell reactivity prediction using support vector machines and string kernels","volume":"12","author":"Tung","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2023062708405491200_btaa1050-B53","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/ni1257","article-title":"T cell receptor recognition of a \u201csuper-bulged\u201d major histocompatibility complex class I-bound peptide","volume":"6","author":"Tynan","year":"2005","journal-title":"Nat. Immunol"},{"key":"2023062708405491200_btaa1050-B54","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1074\/jbc.M111.289488","article-title":"A single autoimmune T cell receptor recognizes more than a million different peptides","volume":"287","author":"Wooldridge","year":"2012","journal-title":"J. Biol. Chem"},{"key":"2023062708405491200_btaa1050-B55","doi-asserted-by":"crossref","first-page":"5581","DOI":"10.4049\/jimmunol.152.11.5581","article-title":"Clonal expansion and persistence of human T cells specific for an lmmunodominant myelin basic protein peptide","volume":"152","author":"Wucherpfennig","year":"1994","journal-title":"J. Immunol"},{"key":"2023062708405491200_btaa1050-B56","doi-asserted-by":"crossref","first-page":"e1006457","DOI":"10.1371\/journal.pcbi.1006457","article-title":"Systematically benchmarking peptide-MHC binding predictors: from synthetic to naturally processed epitopes","volume":"14","author":"Zhao","year":"2018","journal-title":"PLoS Comput. Biol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaa1050\/35383730\/btaa1050.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/36\/22-23\/5377\/50715898\/btaa1050.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/36\/22-23\/5377\/50715898\/btaa1050.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T08:42:00Z","timestamp":1687855320000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/36\/22-23\/5377\/6045943"}},"subtitle":[],"editor":[{"given":"Arne","family":"Elofsson","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2020,12,1]]},"references-count":56,"journal-issue":{"issue":"22-23","published-print":{"date-parts":[[2021,4,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaa1050","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"type":"print","value":"1367-4803"},{"type":"electronic","value":"1367-4811"}],"subject":[],"published-other":{"date-parts":[[2020,12,1]]},"published":{"date-parts":[[2020,12,1]]}}}