{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:38:40Z","timestamp":1740184720277,"version":"3.37.3"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU-ToxRisk project"},{"name":"European Commission under the Horizon 2020 Program","award":["681002"],"award-info":[{"award-number":["681002"]}]},{"name":"European Union Seventh Framework Programme HeCaToS","award":["FP7\/2007-2013"],"award-info":[{"award-number":["FP7\/2007-2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Summary<\/jats:title>\n                  <jats:p>Typical RNA sequencing (RNA-Seq) analyses are performed either at the gene level by summing all reads from the same locus, assuming that all transcripts from a gene make a protein or at the transcript level, assuming that each transcript displays unique function. However, these assumptions are flawed, as a gene can code for different types of transcripts and different transcripts are capable of synthesizing similar, different or no protein. As a consequence, functional changes are not well illustrated by either gene or transcript analyses. We propose to improve RNA-Seq analyses by grouping the transcripts based on their similar functions. We developed FuSe to predict functional similarities using the primary and secondary structure of proteins. To estimate the likelihood of proteins with similar functions, FuSe computes two confidence scores: knowledge (KS) and discovery (DS) for protein pairs. Overlapping protein pairs exhibiting high confidence are grouped to form \u2018similar function protein groups\u2019 and expression is calculated for each functional group. The impact of using FuSe is demonstrated on in vitro cells exposed to paracetamol, which highlight genes responsible for cell adhesion and glycogen regulation which were earlier shown to be not differentially expressed with traditional analysis methods.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The source code is available at https:\/\/github.com\/rajinder4489\/FuSe. Data for APAP exposure are available in the BioStudies database (http:\/\/www.ebi.ac.uk\/biostudies) under accession numbers S-HECA143, S-HECA(158) and S-HECA139.<\/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\/btaa735","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T11:56:13Z","timestamp":1597319773000},"page":"375-381","source":"Crossref","is-referenced-by-count":2,"title":["FuSe: a tool to move RNA-Seq analyses from chromosomal\/gene loci to functional grouping of mRNA transcripts"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3342-2122","authenticated-orcid":false,"given":"Rajinder","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University , Maastricht, 6229ER, The Netherlands"}]},{"given":"Yannick","family":"Schrooders","sequence":"additional","affiliation":[{"name":"Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University , Maastricht, 6229ER, The Netherlands"}]},{"given":"Marcha","family":"Verheijen","sequence":"additional","affiliation":[{"name":"Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University , Maastricht, 6229ER, The Netherlands"}]},{"given":"Adrian","family":"Roth","sequence":"additional","affiliation":[{"name":"Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel , Basel, CH-4070, Switzerland"}]},{"given":"Jos","family":"Kleinjans","sequence":"additional","affiliation":[{"name":"Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University , Maastricht, 6229ER, The Netherlands"}]},{"given":"Florian","family":"Caiment","sequence":"additional","affiliation":[{"name":"Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University , Maastricht, 6229ER, The Netherlands"}]}],"member":"286","published-online":{"date-parts":[[2020,8,19]]},"reference":[{"key":"2023051604084547900_btaa735-B1","doi-asserted-by":"crossref","first-page":"W7","DOI":"10.1093\/nar\/gkq291","article-title":"TranslatorX: multiple alignment of nucleotide sequences guided by amino acid translations","volume":"38","author":"Abascal","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"2023051604084547900_btaa735-B2","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"2023051604084547900_btaa735-B3","doi-asserted-by":"crossref","first-page":"W597","DOI":"10.1093\/nar\/gks400","article-title":"ExPASy: SIB bioinformatics resource portal","volume":"40","author":"Artimo","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2023051604084547900_btaa735-B4","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"2023051604084547900_btaa735-B5","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/0141-1136(89)90262-6","article-title":"Morphological changes in trout hepatocytes exposed to acetaminophen","volume":"28","author":"Blair","year":"1989","journal-title":"Mar. Environ. Res"},{"key":"2023051604084547900_btaa735-B6","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. Biotechnol"},{"key":"2023051604084547900_btaa735-B7","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1186\/1471-2105-10-421","article-title":"BLAST+: architecture and applications","volume":"10","author":"Camacho","year":"2009","journal-title":"BMC Bioinform"},{"key":"2023051604084547900_btaa735-B8","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1093\/bioinformatics\/btx364","article-title":"UpSetR: an R package for the visualization of intersecting sets and their properties","volume":"33","author":"Conway","year":"2017","journal-title":"Bioinformatics"},{"key":"2023051604084547900_btaa735-B9","doi-asserted-by":"crossref","first-page":"8595","DOI":"10.1074\/jbc.M109.089003","article-title":"The E2 ubiquitin-conjugating enzymes direct polyubiquitination to preferred lysines","volume":"285","author":"David","year":"2010","journal-title":"J. Biol. Chem"},{"key":"2023051604084547900_btaa735-B10","doi-asserted-by":"crossref","first-page":"D754","DOI":"10.1093\/nar\/gkx1098","article-title":"Ensembl 2018","volume":"46","author":"Frankish","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2023051604084547900_btaa735-B11","doi-asserted-by":"crossref","first-page":"37541","DOI":"10.1038\/srep37541","article-title":"Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver","volume":"7","author":"Gamal","year":"2017","journal-title":"Sci. Rep"},{"key":"2023051604084547900_btaa735-B12","doi-asserted-by":"crossref","first-page":"e45521","DOI":"10.1371\/journal.pone.0045521","article-title":"Identification of early biomarkers during acetaminophen-induced hepatotoxicity by Fourier transform infrared microspectroscopy","volume":"7","author":"Gautam","year":"2012","journal-title":"PLoS One"},{"key":"2023051604084547900_btaa735-B13","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/prot.20622","article-title":"Does secondary structure determine tertiary structure in proteins?","volume":"61","author":"Gong","year":"2005","journal-title":"Proteins"},{"key":"2023051604084547900_btaa735-B14","first-page":"1","volume-title":"Encyclopedia of Neuroscience","author":"Hegde","year":"2009"},{"key":"2023051604084547900_btaa735-B15","doi-asserted-by":"crossref","first-page":"interactions1002.1","DOI":"10.1186\/gb-2001-2-8-interactions1002","article-title":"Orthologs and paralogs\u2014we need to get it right","volume":"2","author":"Jensen","year":"2001","journal-title":"Genome Biol"},{"key":"2023051604084547900_btaa735-B16","doi-asserted-by":"crossref","first-page":"10775","DOI":"10.1038\/srep10775","article-title":"Relationship between differentially expressed mRNA and mRNA-protein correlations in a xenograft model system","volume":"5","author":"Koussounadis","year":"2015","journal-title":"Sci. Rep"},{"key":"2023051604084547900_btaa735-B17","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s00204-017-2041-7","article-title":"A model-based assay design to reproduce in vivo patterns of acute drug-induced toxicity","volume":"92","author":"Kuepfer","year":"2018","journal-title":"Arch. Toxicol"},{"key":"2023051604084547900_btaa735-B18","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinform"},{"key":"2023051604084547900_btaa735-B19","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2016.03.014","article-title":"On the dependency of cellular protein levels on mRNA abundance","volume":"165","author":"Liu","year":"2016","journal-title":"Cell"},{"key":"2023051604084547900_btaa735-B20","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1586\/14789450.2.5.719","article-title":"Histone structure and nucleosome stability","volume":"2","author":"Mari\u00f1o-Ram\u00edrez","year":"2005","journal-title":"Exp. Rev. Proteomics"},{"key":"2023051604084547900_btaa735-B21","doi-asserted-by":"crossref","first-page":"W597","DOI":"10.1093\/nar\/gkt376","article-title":"Analysis tool web services from the EMBL-EBI","volume":"41","author":"McWilliam","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2023051604084547900_btaa735-B22","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1158\/0008-5472.CAN-06-3071","article-title":"Protein phosphatase-1alpha regulates centrosome splitting through Nek2","volume":"67","author":"Mi","year":"2007","journal-title":"Cancer Res"},{"key":"2023051604084547900_btaa735-B23","doi-asserted-by":"crossref","first-page":"D351","DOI":"10.1093\/nar\/gky1100","article-title":"InterPro in 2019: improving coverage, classification and access to protein sequence annotations","volume":"47","author":"Mitchell","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2023051604084547900_btaa735-B24","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/prot.25415","article-title":"Critical assessment of methods of protein structure prediction (CASP)-Round XII","volume":"86","author":"Moult","year":"2018","journal-title":"Proteins"},{"key":"2023051604084547900_btaa735-B25","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/40618","article-title":"Evolution of genetic redundancy","volume":"388","author":"Nowak","year":"1997","journal-title":"Nature"},{"key":"2023051604084547900_btaa735-B26","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1002\/cbic.201800650","article-title":"A review on quantitative multiplexed proteomics","volume":"20","author":"Pappireddi","year":"2019","journal-title":"ChemBioChem"},{"key":"2023051604084547900_btaa735-B27","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/nbt.2862","article-title":"Sailfish enables alignment-free isoform quantification from RNA-seq reads using lightweight algorithms","volume":"32","author":"Patro","year":"2014","journal-title":"Nat. Biotechnol"},{"key":"2023051604084547900_btaa735-B28","article-title":"Salmon: accurate, versatile and ultrafast quantification from RNA-seq data using lightweight-alignment","author":"Patro","year":"2015","journal-title":"BioRxiv"},{"key":"2023051604084547900_btaa735-B29","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/B978-0-323-03410-4.50009-2","volume-title":"Elsevier's Integrated Biochemistry","author":"Pelley","year":"2007"},{"key":"2023051604084547900_btaa735-B30","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nbt.3122","article-title":"StringTie enables improved reconstruction of a transcriptome from RNA-seq reads","volume":"33","author":"Pertea","year":"2015","journal-title":"Nat. Biotechnol"},{"key":"2023051604084547900_btaa735-B31","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1080\/15548627.2015.1060386","article-title":"ATG16L1 phosphorylation is oppositely regulated by CSNK2\/casein kinase 2 and PPP1\/protein phosphatase 1 which determines the fate of cardiomyocytes during hypoxia\/reoxygenation","volume":"11","author":"Song","year":"2015","journal-title":"Autophagy"},{"key":"2023051604084547900_btaa735-B32","first-page":"27","article-title":"UniProt: a hub for protein information","volume":"43","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2023051604084547900_btaa735-B33"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaa735\/33821986\/btaa735.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/3\/375\/50325981\/btaa735.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/3\/375\/50325981\/btaa735.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T04:10:13Z","timestamp":1684210213000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/37\/3\/375\/5894546"}},"subtitle":[],"editor":[{"given":"Yann","family":"Ponty","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2020,8,19]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,4,20]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaa735","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"type":"print","value":"1367-4803"},{"type":"electronic","value":"1367-4811"}],"subject":[],"published-other":{"date-parts":[[2021,2,1]]},"published":{"date-parts":[[2020,8,19]]}}}