{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T17:58:52Z","timestamp":1772733532476,"version":"3.50.1"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: The translational landscape of diverse cellular systems remains largely uncharacterized. A detailed understanding of the control of gene expression at the level of messenger RNA translation is vital to elucidating a systems-level view of complex molecular programs in the cell. Establishing the degree to which such post-transcriptional regulation can mediate specific phenotypes is similarly critical to elucidating the molecular pathogenesis of diseases such as cancer. Recently, methods for massively parallel sequencing of ribosome-bound fragments of messenger RNA have begun to uncover genome-wide translational control at codon resolution. Despite its promise for deeply characterizing mammalian proteomes, few analytical methods exist for the comprehensive analysis of this paired RNA and ribosome data.<\/jats:p>\n               <jats:p>Results: We describe the Babel framework, an analytical methodology for assessing the significance of changes in translational regulation within cells and between conditions. This approach facilitates the analysis of translation genome-wide while allowing statistically principled gene-level inference. Babel is based on an errors-in-variables regression model that uses the negative binomial distribution and draws inference using a parametric bootstrap approach. We demonstrate the operating characteristics of Babel on simulated data and use its gene-level inference to extend prior analyses significantly, discovering new translationally regulated modules under mammalian target of rapamycin (mTOR) pathway signaling control.<\/jats:p>\n               <jats:p>Availability: The Babel framework is freely available as source code at http:\/\/taylorlab.ucsf.edu\/software_data.html.<\/jats:p>\n               <jats:p>Contact: \u00a0barry.taylor@ucsf.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btt533","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T01:05:55Z","timestamp":1379552755000},"page":"2995-3002","source":"Crossref","is-referenced-by-count":76,"title":["Assessing gene-level translational control from ribosome profiling"],"prefix":"10.1093","volume":"29","author":[{"given":"Adam B.","family":"Olshen","sequence":"first","affiliation":[{"name":"1 Department of Epidemiology and Biostatistics, 2Helen Diller Family Comprehensive Cancer Center, 3Department of Medicine and 4Department of Urology, University of California, San Francisco, CA 94158, USA and 5Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"1 Department of Epidemiology and Biostatistics, 2Helen Diller Family Comprehensive Cancer Center, 3Department of Medicine and 4Department of Urology, University of California, San Francisco, CA 94158, USA and 5Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew C.","family":"Hsieh","sequence":"additional","affiliation":[{"name":"1 Department of Epidemiology and Biostatistics, 2Helen Diller Family Comprehensive Cancer Center, 3Department of Medicine and 4Department of Urology, University of California, San Francisco, CA 94158, USA and 5Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"1 Department of Epidemiology and Biostatistics, 2Helen Diller Family Comprehensive Cancer Center, 3Department of Medicine and 4Department of Urology, University of California, San Francisco, CA 94158, USA and 5Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"1 Department of Epidemiology and Biostatistics, 2Helen Diller Family Comprehensive Cancer Center, 3Department of Medicine and 4Department of Urology, University of California, San Francisco, CA 94158, USA and 5Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig R.","family":"Stumpf","sequence":"additional","affiliation":[{"name":"1 Department of Epidemiology and Biostatistics, 2Helen Diller Family Comprehensive Cancer Center, 3Department of Medicine and 4Department of Urology, University of California, San Francisco, CA 94158, USA and 5Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"1 Department of Epidemiology and Biostatistics, 2Helen Diller Family Comprehensive Cancer Center, 3Department of Medicine and 4Department of Urology, University of California, San Francisco, CA 94158, USA and 5Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Olshen","sequence":"additional","affiliation":[{"name":"1 Department of Epidemiology and Biostatistics, 2Helen Diller Family Comprehensive Cancer Center, 3Department of Medicine and 4Department of Urology, University of California, San Francisco, CA 94158, USA and 5Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Ruggero","sequence":"additional","affiliation":[{"name":"1 Department of Epidemiology and Biostatistics, 2Helen Diller Family Comprehensive Cancer Center, 3Department of Medicine and 4Department of Urology, University of California, San Francisco, CA 94158, USA and 5Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"1 Department of Epidemiology and Biostatistics, 2Helen Diller Family Comprehensive Cancer Center, 3Department of Medicine and 4Department of Urology, University of California, San Francisco, CA 94158, USA and 5Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry S.","family":"Taylor","sequence":"additional","affiliation":[{"name":"1 Department of Epidemiology and Biostatistics, 2Helen Diller Family Comprehensive Cancer Center, 3Department of Medicine and 4Department of Urology, University of California, San Francisco, CA 94158, USA and 5Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"1 Department of Epidemiology and Biostatistics, 2Helen Diller Family Comprehensive Cancer Center, 3Department of Medicine and 4Department of Urology, University of California, San Francisco, CA 94158, USA and 5Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"1 Department of Epidemiology and Biostatistics, 2Helen Diller Family Comprehensive Cancer Center, 3Department of Medicine and 4Department of Urology, University of California, San Francisco, CA 94158, USA and 5Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,9,18]]},"reference":[{"key":"2023012810494938000_btt533-B1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1126\/science.1215704","article-title":"Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish","volume":"336","author":"Bazzini","year":"2012","journal-title":"Science"},{"key":"2023012810494938000_btt533-B2","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1080\/00223980.1972.9924813","article-title":"An additive method for combining probability values from independent experiments","volume":"80","author":"Edgington","year":"1972","journal-title":"J. Psychol."},{"key":"2023012810494938000_btt533-B3","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nature09267","article-title":"Mammalian microRNAs predominantly act to decrease target mRNA levels","volume":"466","author":"Guo","year":"2010","journal-title":"Nature"},{"key":"2023012810494938000_btt533-B4","doi-asserted-by":"crossref","first-page":"240","DOI":"10.2307\/2331961","article-title":"The distribution of means for samples of size n drawn from a population in which the variate takes values between 0 and 1, all such values being equally probable","volume":"19","author":"Hall","year":"1927","journal-title":"Biometrika"},{"key":"2023012810494938000_btt533-B5","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2006-7-s1-s4","article-title":"GENCODE: producing a reference annotation for ENCODE","volume":"7","author":"Harrow","year":"2006","journal-title":"Genome Biol."},{"key":"2023012810494938000_btt533-B6","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature10912","article-title":"The translational landscape of mTOR signalling steers cancer initiation and metastasis","volume":"485","author":"Hsieh","year":"2012","journal-title":"Nature"},{"key":"2023012810494938000_btt533-B7","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1126\/science.1168978","article-title":"Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling","volume":"324","author":"Ingolia","year":"2009","journal-title":"Science"},{"key":"2023012810494938000_btt533-B8","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.cell.2011.10.002","article-title":"Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes","volume":"147","author":"Ingolia","year":"2011","journal-title":"Cell"},{"key":"2023012810494938000_btt533-B9","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/biomet\/19.3-4.225","article-title":"On the frequency distribution of the means of samples from a population having any law of frequency with finite moments, with special reference to Pearson's Type II","volume":"19","author":"Irwin","year":"1927","journal-title":"Biometrika"},{"key":"2023012810494938000_btt533-B10","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012810494938000_btt533-B11","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012810494938000_btt533-B12","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1038\/sj.emboj.7601765","article-title":"Reconstitution reveals the functional core of mammalian eIF3","volume":"26","author":"Masutani","year":"2007","journal-title":"EMBO J."},{"key":"2023012810494938000_btt533-B13","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/gb-2010-11-3-r25","article-title":"A scaling normalization method for differential expression analysis of RNA-seq data","volume":"11","author":"Robinson","year":"2010","journal-title":"Genome Biol."},{"key":"2023012810494938000_btt533-B14","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/biostatistics\/kxm030","article-title":"Small-sample estimation of negative binomial dispersion, with applications to SAGE data","volume":"9","author":"Robinson","year":"2008","journal-title":"Biostatistics"},{"key":"2023012810494938000_btt533-B15","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"2023012810494938000_btt533-B16","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1126\/science.1118977","article-title":"Structural roles for human translation factor eIF3 in initiation of protein synthesis","volume":"310","author":"Siridechadilok","year":"2005","journal-title":"Science"},{"key":"2023012810494938000_btt533-B17","doi-asserted-by":"crossref","DOI":"10.2202\/1544-6115.1027","article-title":"Linear models and empirical bayes methods for assessing differential expression in microarray experiments","volume":"3","author":"Smyth","year":"2004","journal-title":"Stat. Appl. Genet. Mol. Biol."},{"key":"2023012810494938000_btt533-B18","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/1467-9868.00346","article-title":"A direct approach to false discovery rates","volume":"64","author":"Storey","year":"2002","journal-title":"J. R. Statist. Soc. B"},{"key":"2023012810494938000_btt533-B19","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nature11083","article-title":"A unifying model for mTORC1-mediated regulation of mRNA translation","volume":"485","author":"Thoreen","year":"2012","journal-title":"Nature"},{"key":"2023012810494938000_btt533-B20","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/bioinformatics\/btp120","article-title":"TopHat: discovering splice junctions with RNA-Seq","volume":"25","author":"Trapnell","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012810494938000_btt533-B21","doi-asserted-by":"crossref","first-page":"18139","DOI":"10.1073\/pnas.0801313105","article-title":"Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3","volume":"105","author":"Zhou","year":"2008","journal-title":"Proc. Natl Acad. Sci. USA"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/29\/23\/2995\/48899576\/bioinformatics_29_23_2995.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/29\/23\/2995\/48899576\/bioinformatics_29_23_2995.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T12:51:29Z","timestamp":1674910289000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/29\/23\/2995\/248241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9,18]]},"references-count":21,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2013,12,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btt533","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2013,12,1]]},"published":{"date-parts":[[2013,9,18]]}}}