{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T18:51:46Z","timestamp":1771699906112,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1034,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: \u00a0Drosophila melanogaster is a major model organism for investigating the function and interconnection of animal genes in the earliest stages of embryogenesis. Today, images capturing Drosophila gene expression patterns are being produced at a higher throughput than ever before. The analysis of spatial patterns of gene expression is most biologically meaningful when images from a similar time point during development are compared. Thus, the critical first step is to determine the developmental stage of an embryo. This information is also needed to observe and analyze expression changes over developmental time. Currently, developmental stages (time) of embryos in images capturing spatial expression pattern are annotated manually, which is time- and labor-intensive. Embryos are often designated into stage ranges, making the information on developmental time course. This makes downstream analyses inefficient and biological interpretations of similarities and differences in spatial expression patterns challenging, particularly when using automated tools for analyzing expression patterns of large number of images.<\/jats:p><jats:p>Results: Here, we present a new computational approach to annotate developmental stage for Drosophila embryos in the gene expression images. In an analysis of 3724 images, the new approach shows high accuracy in predicting the developmental stage correctly (79%). In addition, it provides a stage score that enables one to more finely annotate each embryo so that they are divided into early and late periods of development within standard stage demarcations. Stage scores for all images containing expression patterns of the same gene enable a direct way to view expression changes over developmental time for any gene. We show that the genomewide-expression-maps generated using images from embryos in refined stages illuminate global gene activities and changes much better, and more refined stage annotations improve our ability to better interpret results when expression pattern matches are discovered between genes.<\/jats:p><jats:p>Availability and implementation: The software package is available for download at: http:\/\/www.public.asu.edu\/\u223cjye02\/Software\/Fly-Project\/.<\/jats:p><jats:p>Contact: \u00a0jieping.ye@asu.edu<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btt648","type":"journal-article","created":{"date-parts":[[2013,12,4]],"date-time":"2013-12-04T02:09:13Z","timestamp":1386122953000},"page":"266-273","source":"Crossref","is-referenced-by-count":12,"title":["Automated annotation of developmental stages of<i>Drosophila<\/i>embryos in images containing spatial patterns of expression"],"prefix":"10.1093","volume":"30","author":[{"given":"Lei","family":"Yuan","sequence":"first","affiliation":[{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Pan","sequence":"additional","affiliation":[{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuiwang","family":"Ji","sequence":"additional","affiliation":[{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"McCutchan","sequence":"additional","affiliation":[{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Hua","family":"Zhou","sequence":"additional","affiliation":[{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart J.","family":"Newfeld","sequence":"additional","affiliation":[{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudhir","family":"Kumar","sequence":"additional","affiliation":[{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieping","family":"Ye","sequence":"additional","affiliation":[{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"1 School of Computing, Informatics, and Decision Systems Engineering, 2Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA, 3National Key Laboratory for Novel Software Technology, Nanjing University, Nanjing 210023, China, 4School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA and 5Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,12,3]]},"reference":[{"key":"2023012710393907900_btt648-B1","volume-title":"Pattern Recognition and Machine Learning","author":"Bishop","year":"2006"},{"key":"2023012710393907900_btt648-B2","doi-asserted-by":"crossref","first-page":"i16","DOI":"10.1093\/bioinformatics\/bts220","article-title":"Joint stage recognition and anatomical annotation of Drosophila gene expression patterns","volume":"28","author":"Cai","year":"2012","journal-title":"Bioinformatics"},{"key":"2023012710393907900_btt648-B3","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-662-22489-2","volume-title":"The Embryonic Development of Drosophila Melanogaster","author":"Campos-Ortega","year":"1997"},{"key":"2023012710393907900_btt648-B4","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nmeth.2082","article-title":"Current challenges in open-source bioimage informatics","volume":"9","author":"Cardona","year":"2012","journal-title":"Nat. Methods"},{"key":"2023012710393907900_btt648-B5","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/bfgp\/els038","article-title":"Functional genomics in Drosophila models of human disease","volume":"11","author":"Chen","year":"2012","journal-title":"Brief. Funct. Genomics"},{"key":"2023012710393907900_btt648-B6","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/0042-6989(80)90065-6","article-title":"Two-dimensional spectral analysis of cortical receptive field profiles","volume":"20","author":"Daugman","year":"1980","journal-title":"Vision Res."},{"key":"2023012710393907900_btt648-B7","first-page":"1871","article-title":"Liblinear: a library for large linear classification","volume":"9","author":"Fan","year":"2008","journal-title":"JMLR"},{"key":"2023012710393907900_btt648-B8","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1364\/JOSAA.4.002379","article-title":"Relations between the statistics of natural images and the response properties of cortical cells","volume":"4","author":"Field","year":"1987","journal-title":"J. Opt. Soc. Am. A"},{"key":"2023012710393907900_btt648-B9","article-title":"A note on the group lasso and a sparse group lasso","volume-title":"Technical report","author":"Friedman","year":"2010"},{"key":"2023012710393907900_btt648-B10","volume-title":"Atlas of Drosophila Development","author":"Hartenstein","year":"1993"},{"key":"2023012710393907900_btt648-B11","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-84858-7","volume-title":"The Elements of Statistical Learning: Data Mining, Inference, and Prediction","author":"Hastie","year":"2009","edition":"2nd edn"},{"key":"2023012710393907900_btt648-B12","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1093\/bioinformatics\/btn347","article-title":"Automated annotation of Drosophila gene expression patterns using a controlled vocabulary","volume":"24","author":"Ji","year":"2008","journal-title":"Bioinformatics"},{"key":"2023012710393907900_btt648-B13","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/nature09634","article-title":"Gene expression divergence recapitulates the developmental hourglass model","volume":"468","author":"Kalinka","year":"2010","journal-title":"Nature"},{"key":"2023012710393907900_btt648-B14","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/dvdy.22749","article-title":"Comparison of embryonic expression within multigene families using the flyexpress discovery platform reveals more spatial than temporal divergence","volume":"241","author":"Konikoff","year":"2012","journal-title":"Dev. Dyn."},{"key":"2023012710393907900_btt648-B15","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/35098564","article-title":"Signalling pathways in Drosophila and vertebrate retinal development","volume":"2","author":"Kumar","year":"2001","journal-title":"Nat. Rev. Genet."},{"key":"2023012710393907900_btt648-B16","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1093\/genetics\/162.4.2037","article-title":"BEST: a novel computational approach for comparing gene expression patterns from early stages of Drosophila melanogaster development","volume":"162","author":"Kumar","year":"2002","journal-title":"Genetics"},{"key":"2023012710393907900_btt648-B17","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1093\/bioinformatics\/btr567","article-title":"Flyexpress: visual mining of spatiotemporal patterns for genes and publications in Drosophila embryogenesis","volume":"27","author":"Kumar","year":"2011","journal-title":"Bioinformatics"},{"key":"2023012710393907900_btt648-B18","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/bts518","article-title":"Exploring spatial patterns of gene expression from fruit fly embryogenesis on the iphone","volume":"28","author":"Kumar","year":"2012","journal-title":"Bioinformatics"},{"key":"2023012710393907900_btt648-B19","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.cell.2007.08.003","article-title":"Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function","volume":"131","author":"L\u00e9cuyer","year":"2007","journal-title":"Cell"},{"key":"2023012710393907900_btt648-B20","doi-asserted-by":"crossref","first-page":"4936","DOI":"10.1073\/pnas.0408031102","article-title":"Gene regulatory networks for development","volume":"102","author":"Levine","year":"2005","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012710393907900_btt648-B21","first-page":"1459","article-title":"Moreau-yosida regularization for grouped tree structure learning","volume":"23","author":"Liu","year":"2010","journal-title":"Adv. Neural Inf. Process. Syst."},{"key":"2023012710393907900_btt648-B22","volume-title":"SLEP: Sparse Learning with Efficient Projections","author":"Liu","year":"2009"},{"key":"2023012710393907900_btt648-B23","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1109\/IRI.2011.6009536","article-title":"Automatic annotation of Drosophila developmental stages using association classification and information integration","volume-title":"Information Reuse and Integration (IRI), 2011 IEEE International Conference on","author":"Meng","year":"2011"},{"key":"2023012710393907900_btt648-B24","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1016\/j.juro.2013.03.010","article-title":"Drosophila melanogaster as an emerging translational model of human nephrolithiasis","volume":"190","author":"Miller","year":"2013","journal-title":"J. Urol."},{"key":"2023012710393907900_btt648-B25","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.devcel.2013.01.017","article-title":"Three-dimensional epithelial morphogenesis in the developing Drosophila egg","volume":"24","author":"Osterfield","year":"2013","journal-title":"Dev. Cell"},{"key":"2023012710393907900_btt648-B26","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1186\/1471-2121-8-S1-S7","article-title":"Automatic image analysis for gene expression patterns of fly embryos","volume":"8","author":"Peng","year":"2007","journal-title":"BMC Cell Biol."},{"key":"2023012710393907900_btt648-B27","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/nrg947","article-title":"Evolution of development in closely related species of flies and worms","volume":"3","author":"Simpson","year":"2002","journal-title":"Nat. Rev. Genet."},{"key":"2023012710393907900_btt648-B28","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.2517-6161.1996.tb02080.x","article-title":"Regression shrinkage and selection via the lasso","volume":"58","author":"Tibshirani","year":"1996","journal-title":"J. R. Stat. Soc. Series B (Methodol)"},{"key":"2023012710393907900_btt648-B29","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2002-3-12-research0088","article-title":"Systematic determination of patterns of gene expression during Drosophila embryogenesis","volume":"3","author":"Tomancak","year":"2002","journal-title":"Genome Biol."},{"key":"2023012710393907900_btt648-B30","doi-asserted-by":"crossref","first-page":"R145","DOI":"10.1186\/gb-2007-8-7-r145","article-title":"Global analysis of patterns of gene expression during Drosophila embryogenesis","volume":"8","author":"Tomancak","year":"2007","journal-title":"Genome Biol."},{"key":"2023012710393907900_btt648-B31","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4757-3264-1","volume-title":"The Nature of Statistical Learning Theory","author":"Vapnik","year":"2000","edition":"2nd edn"},{"key":"2023012710393907900_btt648-B32","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1038\/nmeth.1431","article-title":"Visualization of image data from cells to organisms","volume":"7","author":"Walter","year":"2010","journal-title":"Nat. Methods"},{"key":"2023012710393907900_btt648-B33","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nrg1502","article-title":"The phenogenetic logic of life","volume":"6","author":"Weiss","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"2023012710393907900_btt648-B34","doi-asserted-by":"crossref","first-page":"3819","DOI":"10.1007\/s00018-012-1022-5","article-title":"What model organisms and interactomics can reveal about the genetics of human obesity","volume":"69","author":"Williams","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"2023012710393907900_btt648-B35","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.devcel.2008.09.008","article-title":"A combinatorial code for pattern formation in Drosophila oogenesis","volume":"15","author":"Yakoby","year":"2008","journal-title":"Dev. Cell"},{"key":"2023012710393907900_btt648-B36","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1145\/2408736.2408739","article-title":"Sparse methods for biomedical data","volume":"14","author":"Ye","year":"2012","journal-title":"ACM SIGKDD Explorations Newsletter"},{"key":"2023012710393907900_btt648-B37","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1142\/9781860947575_0035","article-title":"Classification of Drosophila embryonic developmental stage range based on gene expression pattern images","volume-title":"Proceedings of the Computational Systems Bioinformatics Conference","author":"Ye","year":"2006"},{"key":"2023012710393907900_btt648-B38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1145\/1342320.1342324","article-title":"Developmental stage annotation of Drosophila gene expression pattern images via an entire solution path for LDA","volume":"2","author":"Ye","year":"2008","journal-title":"ACM Trans. Knowl. Discov. Data"},{"key":"2023012710393907900_btt648-B39","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1467-9868.2005.00532.x","article-title":"Model selection and estimation in regression with grouped variables","volume":"68","author":"Yuan","year":"2006","journal-title":"J. R. Stat. Soc. Series B. Stat. Methodol."},{"key":"2023012710393907900_btt648-B40","doi-asserted-by":"crossref","DOI":"10.1201\/b12207","volume-title":"Ensemble Methods: Foundations and Algorithms","author":"Zhou","year":"2012"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/30\/2\/266\/48915152\/bioinformatics_30_2_266.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/30\/2\/266\/48915152\/bioinformatics_30_2_266.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T22:06:11Z","timestamp":1716242771000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/30\/2\/266\/222687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,3]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,1,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btt648","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2014,1,15]]},"published":{"date-parts":[[2013,12,3]]}}}