{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T11:45:40Z","timestamp":1768823140235,"version":"3.49.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"S9","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103449"],"award-info":[{"award-number":["P20GM103449"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Alternative splicing isoforms have been reported as a new and robust class of diagnostic biomarkers. Over 95% of human genes are estimated to be alternatively spliced as a powerful means of producing functionally diverse proteins from a single gene. The emergence of next-generation sequencing technologies, especially RNA-seq, provides novel insights into large-scale detection and analysis of alternative splicing at the transcriptional level. Advances in Proteomic Technologies such as liquid chromatography coupled tandem mass spectrometry (LC\u2013MS\/MS), have shown tremendous power for the parallel characterization of large amount of proteins in biological samples. Although poor correspondence has been generally found from previous qualitative comparative analysis between proteomics and microarray data, significantly higher degrees of correlation have been observed at the level of exon. Combining protein and RNA data by searching LC\u2013MS\/MS data against a customized protein database from RNA-Seq may produce a subset of alternatively spliced protein isoform candidates that have higher confidence.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We developed a bioinformatics workflow to discover alternative splicing biomarkers from LC\u2013MS\/MS using RNA-Seq. First, we retrieved high confident, novel alternative splicing biomarkers from the breast cancer RNA-Seq database. Then, we translated these sequences into in silico<jats:italic> Isoform Junction Peptides<\/jats:italic>, and created a customized alternative splicing database for MS searching. Lastly, we ran the Open Mass spectrometry Search Algorithm against the customized alternative splicing database with breast cancer plasma proteome. Twenty six alternative splicing biomarker peptides with one single intron event and one exon skipping event were identified. Further interpretation of biological pathways with our Integrated Pathway Analysis Database showed that these 26 peptides are associated with Cancer, Signaling, Metabolism, Regulation, Immune System and Hemostasis pathways, which are consistent with the 256 alternative splicing biomarkers from the RNA-Seq.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This paper presents a bioinformatics workflow for using RNA-seq data to discover novel alternative splicing biomarkers from the breast cancer proteome. As a complement to synthetic alternative splicing database technique for alternative splicing identification, this method combines the advantages of two platforms: mass spectrometry and next generation sequencing and can help identify potentially highly sample-specific alternative splicing isoform biomarkers at early-stage of cancer.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12859-020-03824-8","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T10:03:49Z","timestamp":1606989829000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Identification of novel alternative splicing biomarkers for breast cancer with LC\/MS\/MS and RNA-Seq"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3502-1808","authenticated-orcid":false,"given":"Fan","family":"Zhang","sequence":"first","affiliation":[]},{"given":"Chris K.","family":"Deng","sequence":"additional","affiliation":[]},{"given":"Mu","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Bin","family":"Deng","sequence":"additional","affiliation":[]},{"given":"Robert","family":"Barber","sequence":"additional","affiliation":[]},{"given":"Gang","family":"Huang","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"key":"3824_CR1","unstructured":"U.S. Breast Cancer Statistics. https:\/\/www.breastcancer.org\/symptoms\/understand_bc\/statistics. Accessed 8 April 2020"},{"issue":"Suppl 7","key":"3824_CR2","doi-asserted-by":"publisher","first-page":"S10","DOI":"10.1186\/1753-6561-7-S7-S10","volume":"7","author":"F Zhang","year":"2013","unstructured":"Zhang F, Chen J, Wang M, Drabier R. A neural network approach to multi-biomarker panel discovery by high-throughput plasma proteomics profiling of breast cancer. BMC Proc. 2013;7(Suppl 7):S10.","journal-title":"BMC Proc"},{"issue":"4","key":"3824_CR3","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1155\/2010\/705847","volume":"28","author":"GS Omenn","year":"2010","unstructured":"Omenn GS, Yocum AK, Menon R. Alternative splice variants, a new class of protein cancer biomarker candidates: findings in pancreatic cancer and breast cancer with systems biology implications. Dis Mark. 2010;28(4):241\u201351.","journal-title":"Dis Mark"},{"key":"3824_CR4","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.gene.2019.02.072","volume":"699","author":"PG Adamopoulos","year":"2019","unstructured":"Adamopoulos PG, Mavrogiannis AV, Kontos CK, Scorilas A. Novel alternative splice variants of the human protein arginine methyltransferase 1 (PRMT1) gene, discovered using next-generation sequencing. Gene. 2019;699:135\u201344.","journal-title":"Gene"},{"key":"3824_CR5","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.gene.2019.05.022","volume":"706","author":"X Xu","year":"2019","unstructured":"Xu X, Yang J, Zhou W, Wang L, Lu Q, Wang X, Hang D, Liu X. Genetic variations within alternative splicing associated genes are associated with breast cancer susceptibility in Chinese women. Gene. 2019;706:140\u20135.","journal-title":"Gene"},{"issue":"3","key":"3824_CR6","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/nrm3525","volume":"14","author":"AR Kornblihtt","year":"2013","unstructured":"Kornblihtt AR, Schor IE, Allo M, Dujardin G, Petrillo E, Munoz MJ. Alternative splicing: a pivotal step between eukaryotic transcription and translation. Nat Rev Mol Cell Biol. 2013;14(3):153\u201365.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"3824_CR7","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/ncomms1892","volume":"3","author":"T Yae","year":"2012","unstructured":"Yae T, Tsuchihashi K, Ishimoto T, Motohara T, Yoshikawa M, Yoshida GJ, Wada T, Masuko T, Mogushi K, Tanaka H, et al. Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell. Nat Commun. 2012;3:883.","journal-title":"Nat Commun"},{"issue":"7","key":"3824_CR8","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1158\/1541-7786.MCR-09-0528","volume":"8","author":"A Lapuk","year":"2010","unstructured":"Lapuk A, Marr H, Jakkula L, Pedro H, Bhattacharya S, Purdom E, Hu Z, Simpson K, Pachter L, Durinck S, et al. Exon-level microarray analyses identify alternative splicing programs in breast cancer. Mol Cancer Res. 2010;8(7):961\u201374.","journal-title":"Mol Cancer Res"},{"issue":"14","key":"3824_CR9","doi-asserted-by":"publisher","first-page":"3363","DOI":"10.1182\/blood-2008-05-160325","volume":"113","author":"ML Yamamoto","year":"2009","unstructured":"Yamamoto ML, Clark TA, Gee SL, Kang JA, Schweitzer AC, Wickrema A, Conboy JG. Alternative pre-mRNA splicing switches modulate gene expression in late erythropoiesis. Blood. 2009;113(14):3363\u201370.","journal-title":"Blood"},{"issue":"1","key":"3824_CR10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nrg2484","volume":"10","author":"Z Wang","year":"2009","unstructured":"Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2009;10(1):57\u201363.","journal-title":"Nat Rev Genet"},{"key":"3824_CR11","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1038\/srep01689","volume":"3","author":"J Eswaran","year":"2013","unstructured":"Eswaran J, Horvath A, Godbole S, Reddy SD, Mudvari P, Ohshiro K, Cyanam D, Nair S, Fuqua SA, Polyak K, et al. RNA sequencing of cancer reveals novel splicing alterations. Sci Rep. 2013;3:1689.","journal-title":"Sci Rep"},{"issue":"18","key":"3824_CR12","doi-asserted-by":"publisher","first-page":"2300","DOI":"10.1093\/bioinformatics\/btt396","volume":"29","author":"LH LeGault","year":"2013","unstructured":"LeGault LH, Dewey CN. Inference of alternative splicing from RNA-Seq data with probabilistic splice graphs. Bioinformatics. 2013;29(18):2300\u201310.","journal-title":"Bioinformatics"},{"issue":"2","key":"3824_CR13","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1093\/nar\/gkq817","volume":"39","author":"S Liu","year":"2011","unstructured":"Liu S, Lin L, Jiang P, Wang D, Xing Y. A comparison of RNA-Seq and high-density exon array for detecting differential gene expression between closely related species. Nucleic Acids Res. 2011;39(2):578\u201388.","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"3824_CR14","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1055\/s-2007-981458","volume":"115","author":"M Vogeser","year":"2007","unstructured":"Vogeser M, Parhofer KG. Liquid chromatography tandem-mass spectrometry (LC\u2013MS\/MS)\u2014technique and applications in endocrinology. Exp Clin Endocrinol Diabetes. 2007;115(9):559\u201370.","journal-title":"Exp Clin Endocrinol Diabetes"},{"issue":"Suppl 6","key":"3824_CR15","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1186\/1471-2105-11-S6-S7","volume":"11","author":"A Zhou","year":"2010","unstructured":"Zhou A, Zhang F, Chen JY. PEPPI: a peptidomic database of human protein isoforms for proteomics experiments. BMC Bioinform. 2010;11(Suppl 6):S7.","journal-title":"BMC Bioinform"},{"issue":"Suppl 14","key":"3824_CR16","doi-asserted-by":"publisher","first-page":"S13","DOI":"10.1186\/1471-2105-14-S14-S13","volume":"14","author":"F Zhang","year":"2013","unstructured":"Zhang F, Drabier R. SASD: the Synthetic Alternative Splicing Database for identifying novel isoform from proteomics. BMC Bioinform. 2013;14(Suppl 14):S13.","journal-title":"BMC Bioinform"},{"issue":"12","key":"3824_CR17","first-page":"1512","volume":"5","author":"AR de Sousa","year":"2009","unstructured":"de Sousa AR, Penalva LO, Marcotte EM, Vogel C. Global signatures of protein and mRNA expression levels. Mol BioSyst. 2009;5(12):1512\u201326.","journal-title":"Mol BioSyst"},{"issue":"24","key":"3824_CR18","doi-asserted-by":"publisher","first-page":"3966","DOI":"10.1016\/j.febslet.2009.10.036","volume":"583","author":"T Maier","year":"2009","unstructured":"Maier T, Guell M, Serrano L. Correlation of mRNA and protein in complex biological samples. FEBS Lett. 2009;583(24):3966\u201373.","journal-title":"FEBS Lett"},{"issue":"6","key":"3824_CR19","doi-asserted-by":"publisher","first-page":"e1001393","DOI":"10.1371\/journal.pgen.1001393","volume":"7","author":"A Ghazalpour","year":"2011","unstructured":"Ghazalpour A, Bennett B, Petyuk VA, Orozco L, Hagopian R, Mungrue IN, Farber CR, Sinsheimer J, Kang HM, Furlotte N, et al. Comparative analysis of proteome and transcriptome variation in mouse. PLoS Genet. 2011;7(6):e1001393.","journal-title":"PLoS Genet"},{"issue":"4","key":"3824_CR20","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nrg3185","volume":"13","author":"C Vogel","year":"2012","unstructured":"Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet. 2012;13(4):227\u201332.","journal-title":"Nat Rev Genet"},{"issue":"2","key":"3824_CR21","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1021\/pr200766z","volume":"11","author":"X Wang","year":"2012","unstructured":"Wang X, Slebos RJ, Wang D, Halvey PJ, Tabb DL, Liebler DC, Zhang B. Protein identification using customized protein sequence databases derived from RNA-Seq data. J Proteome Res. 2012;11(2):1009\u201317.","journal-title":"J Proteome Res"},{"issue":"8","key":"3824_CR22","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.1074\/mcp.O113.028142","volume":"12","author":"GM Sheynkman","year":"2013","unstructured":"Sheynkman GM, Shortreed MR, Frey BL, Smith LM. Discovery and mass spectrometric analysis of novel splice-junction peptides using RNA-Seq. Mol Cell Proteom. 2013;12(8):2341\u201353.","journal-title":"Mol Cell Proteom"},{"issue":"5","key":"3824_CR23","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1093\/bfgp\/eln031","volume":"7","author":"M Wang","year":"2008","unstructured":"Wang M, You J, Bemis KG, Tegeler TJ, Brown DP. Label-free mass spectrometry-based protein quantification technologies in proteomic analysis. Brief Funct Genomics Proteom. 2008;7(5):329\u201339.","journal-title":"Brief Funct Genomics Proteom"},{"key":"3824_CR24","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/978-1-61779-424-7_16","volume":"815","author":"M Wang","year":"2012","unstructured":"Wang M, You J. Mass spectrometry for protein quantification in biomarker discovery. Methods Mol Biol. 2012;815:199\u2013225.","journal-title":"Methods Mol Biol"},{"issue":"6","key":"3824_CR25","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1101\/gr.229102","volume":"12","author":"WJ Kent","year":"2002","unstructured":"Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D. The human genome browser at UCSC. Genome Res. 2002;12(6):996\u20131006.","journal-title":"Genome Res"},{"issue":"Suppl 15","key":"3824_CR26","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1186\/1471-2105-13-S15-S7","volume":"13","author":"F Zhang","year":"2012","unstructured":"Zhang F, Drabier R. IPAD: the integrated pathway analysis database for systematic enrichment analysis. BMC Bioinform. 2012;13(Suppl 15):S7.","journal-title":"BMC Bioinform"},{"issue":"9","key":"3824_CR27","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1093\/molbev\/mss100","volume":"29","author":"I Ezkurdia","year":"2012","unstructured":"Ezkurdia I, del Pozo A, Frankish A, Rodriguez JM, Harrow J, Ashman K, Valencia A, Tress ML. Comparative proteomics reveals a significant bias toward alternative protein isoforms with conserved structure and function. Mol Biol Evol. 2012;29(9):2265\u201383.","journal-title":"Mol Biol Evol"},{"issue":"Suppl 11","key":"3824_CR28","doi-asserted-by":"publisher","first-page":"S14","DOI":"10.1186\/1471-2105-11-S11-S14","volume":"11","author":"K Ning","year":"2010","unstructured":"Ning K, Nesvizhskii AI. The utility of mass spectrometry-based proteomic data for validation of novel alternative splice forms reconstructed from RNA-Seq data: a preliminary assessment. BMC Bioinform. 2010;11(Suppl 11):S14.","journal-title":"BMC Bioinform"},{"issue":"10","key":"3824_CR29","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1158\/1055-9965.EPI-07-0420","volume":"16","author":"H Zhang","year":"2007","unstructured":"Zhang H, Chan DW. Cancer biomarker discovery in plasma using a tissue-targeted proteomic approach. Cancer Epidemiol Biomark Prev. 2007;16(10):1915\u20137.","journal-title":"Cancer Epidemiol Biomark Prev"},{"issue":"4","key":"3824_CR30","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1021\/pr0500657","volume":"4","author":"JM Jacobs","year":"2005","unstructured":"Jacobs JM, Adkins JN, Qian WJ, Liu T, Shen Y, Camp DG 2nd, Smith RD. Utilizing human blood plasma for proteomic biomarker discovery. J Proteome Res. 2005;4(4):1073\u201385.","journal-title":"J Proteome Res"},{"key":"3824_CR31","doi-asserted-by":"publisher","first-page":"2643","DOI":"10.1158\/1078-0432.CCR-13-2933","volume":"20","author":"JA Beaver","year":"2014","unstructured":"Beaver JA, Jelovac D, Balukrishna S, Cochran R, Croessmann S, Zabransky D, Wong HY, Valda Toro P, Cidado J, Blair BG, et al. Detection of cancer DNA in plasma of early stage breast cancer patients. Clin Cancer Res. 2014;20:2643\u201350.","journal-title":"Clin Cancer Res"},{"issue":"Suppl 1","key":"3824_CR32","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1186\/1755-8794-6-S1-S4","volume":"6","author":"F Zhang","year":"2013","unstructured":"Zhang F, Kaufman HL, Deng Y, Drabier R. Recursive SVM biomarker selection for early detection of breast cancer in peripheral blood. BMC Med Genomics. 2013;6(Suppl 1):S4.","journal-title":"BMC Med Genomics"},{"issue":"9","key":"3824_CR33","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1093\/bioinformatics\/btp120","volume":"25","author":"C Trapnell","year":"2009","unstructured":"Trapnell C, Pachter L, Salzberg SL. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics. 2009;25(9):1105\u201311.","journal-title":"Bioinformatics"},{"issue":"2","key":"3824_CR34","doi-asserted-by":"publisher","first-page":"R34","DOI":"10.1186\/gb-2014-15-2-r34","volume":"15","author":"S Hoffmann","year":"2014","unstructured":"Hoffmann S, Otto C, Doose G, Tanzer A, Langenberger D, Christ S, Kunz M, Holdt L, Teupser D, Hackermueller J, et al. A multi-split mapping algorithm for circular RNA, splicing, trans-splicing, and fusion detection. Genome Biol. 2014;15(2):R34.","journal-title":"Genome Biol"},{"issue":"11","key":"3824_CR35","doi-asserted-by":"publisher","first-page":"e79298","DOI":"10.1371\/journal.pone.0079298","volume":"8","author":"KR Kalari","year":"2013","unstructured":"Kalari KR, Necela BM, Tang X, Thompson KJ, Lau M, Eckel-Passow JE, Kachergus JM, Anderson SK, Sun Z, Baheti S, et al. An integrated model of the transcriptome of HER2-positive breast cancer. PLoS ONE. 2013;8(11):e79298.","journal-title":"PLoS ONE"},{"issue":"3","key":"3824_CR36","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nprot.2012.016","volume":"7","author":"C Trapnell","year":"2012","unstructured":"Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, Pimentel H, Salzberg SL, Rinn JL, Pachter L. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012;7(3):562\u201378.","journal-title":"Nat Protoc"},{"issue":"3","key":"3824_CR37","doi-asserted-by":"publisher","first-page":"R25","DOI":"10.1186\/gb-2009-10-3-r25","volume":"10","author":"B Langmead","year":"2009","unstructured":"Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10(3):R25.","journal-title":"Genome Biol"},{"issue":"16","key":"3824_CR38","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R. Genome Project Data Processing S: The Sequence Alignment\/Map format and SAMtools. Bioinformatics. 2009;25(16):2078\u20139.","journal-title":"Bioinformatics"},{"issue":"Database issue","key":"3824_CR39","doi-asserted-by":"publisher","first-page":"D749","DOI":"10.1093\/nar\/gkt1196","volume":"42","author":"P Flicek","year":"2014","unstructured":"Flicek P, Amode MR, Barrell D, Beal K, Billis K, Brent S, Carvalho-Silva D, Clapham P, Coates G, Fitzgerald S, et al. Ensembl 2014. Nucleic Acids Res. 2014;42(Database issue):D749-755.","journal-title":"Nucleic Acids Res"},{"issue":"16","key":"3824_CR40","doi-asserted-by":"publisher","first-page":"9440","DOI":"10.1073\/pnas.1530509100","volume":"100","author":"JD Storey","year":"2003","unstructured":"Storey JD, Tibshirani R. Statistical significance for genomewide studies. Proc Natl Acad Sci U S A. 2003;100(16):9440\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"Database issue","key":"3824_CR41","first-page":"D48","volume":"41","author":"P Flicek","year":"2013","unstructured":"Flicek P, Ahmed I, Amode MR, Barrell D, Beal K, Brent S, Carvalho-Silva D, Clapham P, Coates G, Fairley S, et al. Ensembl 2013. Nucleic Acids Res. 2013;41(Database issue):D48-55.","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"3824_CR42","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1021\/pr0499491","volume":"3","author":"LY Geer","year":"2004","unstructured":"Geer LY, Markey SP, Kowalak JA, Wagner L, Xu M, Maynard DM, Yang X, Shi W, Bryant SH. Open mass spectrometry search algorithm. J Proteome Res. 2004;3(5):958\u201364.","journal-title":"J Proteome Res"},{"issue":"9","key":"3824_CR43","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1074\/mcp.M600469-MCP200","volume":"6","author":"BM Balgley","year":"2007","unstructured":"Balgley BM, Laudeman T, Yang L, Song T, Lee CS. Comparative evaluation of tandem MS search algorithms using a target-decoy search strategy. Mol Cell Proteom. 2007;6(9):1599\u2013608.","journal-title":"Mol Cell Proteom"},{"issue":"14","key":"3824_CR44","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1186\/1471-2105-13-S15-S7","volume":"13","author":"F Zhang","year":"2012","unstructured":"Zhang F, Drabier R. IPAD: the integrated pathway analysis database for systematic enrichment analysis. BMC Bioinform. 2012;13(14):S7.","journal-title":"BMC Bioinform"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-020-03824-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12859-020-03824-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-020-03824-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T10:05:14Z","timestamp":1606989914000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-020-03824-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":44,"journal-issue":{"issue":"S9","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["3824"],"URL":"https:\/\/doi.org\/10.1186\/s12859-020-03824-8","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"14 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This project was approved by research ethics committee of the Indiana University-Purdue University Indianapolis (approval No. 0703\u201329). No administrative permissions were required to access the plasma protein data from the Hoosier Oncology Group.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"541"}}