{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:43:45Z","timestamp":1753875825345,"version":"3.41.2"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy and Competitiveness"},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["PID2019-108096RB-C22","PID2022-140047OB-C22"],"award-info":[{"award-number":["PID2019-108096RB-C22","PID2022-140047OB-C22"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Knowledge of the specific cell types affected by genetic alterations in rare diseases is crucial for advancing diagnostics and treatments. Despite significant progress, the cell types involved in the majority of rare disease manifestations remain largely unknown. In this study, we integrated scRNA-seq data from non-diseased samples with known genetic disorder genes and phenotypic information to predict the specific cell types disrupted by pathogenic mutations for 482 disease phenotypes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found significant phenotype-cell type associations focusing on differential expression and co-expression mechanisms. Our analysis revealed that 13% of the associations documented in the literature were captured through differential expression, while 42% were elucidated through co-expression analysis, also uncovering potential new associations. These findings underscore the critical role of cellular context in disease manifestation and highlight the potential of single-cell data for the development of cell-aware diagnostics and targeted therapies for rare diseases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>All code generated in this work is available at https:\/\/github.com\/SergioAlias\/sc-coex<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae646","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T05:56:24Z","timestamp":1730181384000},"source":"Crossref","is-referenced-by-count":0,"title":["Differential expression and co-expression reveal cell types relevant to genetic disorder phenotypes"],"prefix":"10.1093","volume":"40","author":[{"given":"Sergio","family":"Al\u00edas-Segura","sequence":"first","affiliation":[{"name":"Computational Systems Biology Group, Centro Nacional de Biotecnolog\u00eda (CNB-CSIC) , Madrid, 28049,","place":["Spain"]},{"name":"Department of Molecular Biology and Biochemistry, Science Faculty, University of M\u00e1laga , M\u00e1laga, 29071,","place":["Spain"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2646-6226","authenticated-orcid":false,"given":"Florencio","family":"Pazos","sequence":"additional","affiliation":[{"name":"Computational Systems Biology Group, Centro Nacional de Biotecnolog\u00eda (CNB-CSIC) , Madrid, 28049,","place":["Spain"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6911-1591","authenticated-orcid":false,"given":"Monica","family":"Chagoyen","sequence":"additional","affiliation":[{"name":"Computational Systems Biology Group, Centro Nacional de Biotecnolog\u00eda (CNB-CSIC) , Madrid, 28049,","place":["Spain"]}]}],"member":"286","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"2024110904310884400_btae646-B1","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1101\/gr.275430.121","article-title":"Applications of single-cell genomics and computational strategies to study common disease and population-level variation","volume":"31","author":"Auerbach","year":"2021","journal-title":"Genome Res"},{"key":"2024110904310884400_btae646-B2","doi-asserted-by":"crossref","first-page":"e1003632","DOI":"10.1371\/journal.pcbi.1003632","article-title":"Comparative analysis of human tissue interactomes reveals factors leading to tissue-specific manifestation of hereditary diseases","volume":"10","author":"Barshir","year":"2014","journal-title":"PLoS Comput Biol"},{"key":"2024110904310884400_btae646-B3","doi-asserted-by":"crossref","first-page":"100219","DOI":"10.1016\/j.xcrm.2021.100219","article-title":"A single-cell atlas of the healthy breast tissues reveals clinically relevant clusters of breast epithelial cells","volume":"2","author":"Bhat-Nakshatri","year":"2021","journal-title":"Cell Rep Med"},{"key":"2024110904310884400_btae646-B4","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1056\/NEJMra1603471","article-title":"Amyotrophic lateral sclerosis","volume":"377","author":"Brown","year":"2017","journal-title":"N Engl J Med"},{"key":"2024110904310884400_btae646-B5","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s00431-011-1452-3","article-title":"Educational paper. 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