{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T15:48:51Z","timestamp":1769788131538,"version":"3.49.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2016,12,23]],"date-time":"2016-12-23T00:00:00Z","timestamp":1482451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["11401110, 61532014 and 91530113"],"award-info":[{"award-number":["11401110, 61532014 and 91530113"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hubei Provincial Natural Science Foundation of China","award":["2015CFA010"],"award-info":[{"award-number":["2015CFA010"]}]},{"name":"Research Center Foundation of School of Automation of China University of Geosciences","award":["AU2015CJ008"],"award-info":[{"award-number":["AU2015CJ008"]}]},{"name":"Fundamental Research Funds for the Central Universities, China University of Geosciences"},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong","doi-asserted-by":"crossref","award":["2013KJCX0086"],"award-info":[{"award-number":["2013KJCX0086"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hong Kong Research Grants Council","award":["HKBU5\/CRF\/11G"],"award-info":[{"award-number":["HKBU5\/CRF\/11G"]}]},{"name":"Project CityU","award":["11214814"],"award-info":[{"award-number":["11214814"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2016M600769"],"award-info":[{"award-number":["2016M600769"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Cell fate specification plays a key role to generate distinct cell types during metazoan development. However, most of the underlying signaling networks at cellular level are not well understood. Availability of time lapse single-cell gene expression data collected throughout Caenorhabditis elegans embryogenesis provides an excellent opportunity for investigating signaling networks underlying cell fate specification at systems, cellular and molecular levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We propose a framework to infer signaling networks at cellular level by exploring the single-cell gene expression data. Through analyzing the expression data of nhr-25, a hypodermis-specific transcription factor, in every cells of both wild-type and mutant C.elegans embryos through RNAi against 55 genes, we have inferred a total of 23 genes that regulate (activate or inhibit) nhr-25 expression in cell-specific fashion. We also infer the signaling pathways consisting of each of these genes and nhr-25 based on a probabilistic graphical model for the selected five founder cells, \u2018ABarp\u2019, \u2018ABpla\u2019, \u2018ABpra\u2019, \u2018Caa\u2019 and \u2018Cpa\u2019, which express nhr-25 and mostly develop into hypodermis. By integrating the inferred pathways, we reconstruct five signaling networks with one each for the five founder cells. Using RNAi gene knockdown as a validation method, the inferred networks are able to predict the effects of the knockdown genes. These signaling networks in the five founder cells are likely to ensure faithful hypodermis cell fate specification in C.elegans at cellular level.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and Implementation<\/jats:title>\n                  <jats:p>All source codes and data are available at the github repository https:\/\/github.com\/xthuang226\/Worm_Single_Cell_Data_and_Codes.git.<\/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\/btw796","type":"journal-article","created":{"date-parts":[[2016,12,14]],"date-time":"2016-12-14T12:05:35Z","timestamp":1481717135000},"page":"1528-1535","source":"Crossref","is-referenced-by-count":9,"title":["Inference of cellular level signaling networks using single-cell gene expression data in <i>Caenorhabditis elegans<\/i> reveals mechanisms of cell fate specification"],"prefix":"10.1093","volume":"33","author":[{"given":"Xiao-Tai","family":"Huang","sequence":"first","affiliation":[{"name":"School of Computer Science and Technology, Xidian University, Xi\u2019an, Shaanxi, China"},{"name":"Department of Electronic Engineering, City University of Hong Kong, Hong Kong, China"}]},{"given":"Yuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Automation, China University of Geosciences, Wuhan, China"},{"name":"Hubei Key Laboratory of Advanced Control and Intelligent Automation for Complex Systems"}]},{"given":"Lai Hang Leanne","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Electronic Engineering, City University of Hong Kong, Hong Kong, China"}]},{"given":"Zhongying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biology, Hong Kong Baptist University, Hong Kong, China"}]},{"given":"Hong","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Electronic Engineering, City University of Hong Kong, Hong Kong, China"}]}],"member":"286","published-online":{"date-parts":[[2016,12,29]]},"reference":[{"key":"2023020205103523100_btw796-B1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.devcel.2006.06.003","article-title":"Crosstalk between a nuclear receptor and beta-catenin signaling decides cell fates in the C. elegans somatic gonad","volume":"11","author":"Asahina","year":"2006","journal-title":"Dev. 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