{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T06:31:17Z","timestamp":1744785077380,"version":"3.37.3"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1661331"],"award-info":[{"award-number":["1661331"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"USDA","doi-asserted-by":"publisher","award":["2016-51181-25408"],"award-info":[{"award-number":["2016-51181-25408"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,13]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>Computer inference of biological mechanisms is increasingly approachable due to dynamically rich data sources such as single-cell genomics. Inferred molecular interactions can prioritize hypotheses for wet-lab experiments to expedite biological discovery. However, complex data often come with unwanted biological or technical variations, exposing biases over marginal distribution and sample size in current methods to favor spurious causal relationships.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Considering function direction and strength as evidence for causality, we present an adapted functional chi-squared test (AdpFunChisq) that rewards functional patterns over non-functional or independent patterns. On synthetic and three biology datasets, we demonstrate the advantages of AdpFunChisq over 10 methods on overcoming biases that give rise to wide fluctuations in the performance of alternative approaches. On single-cell multiomics data of multiple phenotype acute leukemia, we found that the T-cell surface glycoprotein CD3 delta chain may causally mediate specific genes in the viral carcinogenesis pathway. Using the causality-by-functionality principle, AdpFunChisq offers a viable option for robust causal inference in dynamical systems.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>The AdpFunChisq test is implemented in the R package \u2018FunChisq\u2019 (2.5.2 or above) at https:\/\/cran.r-project.org\/package=FunChisq. All other source code along with pre-processed data is available at Code Ocean https:\/\/doi.org\/10.24433\/CO.2907738.v1<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary materials are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btac206","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T13:42:58Z","timestamp":1649252578000},"page":"2818-2825","source":"Crossref","is-referenced-by-count":3,"title":["Overcoming biases in causal inference of molecular interactions"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0930-1582","authenticated-orcid":false,"given":"Sajal","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Computer Science, New Mexico State University , Las Cruces, NM 88003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6883-6547","authenticated-orcid":false,"given":"Mingzhou","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Computer Science, New Mexico State University , Las Cruces, NM 88003, USA"},{"name":"Molecular Biology and Interdisciplinary Life Sciences Graduate Program, New Mexico State University , Las Cruces, NM 88003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"2023040600413515800_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-019-1795-z","article-title":"A comparison of automatic cell identification methods for single-cell RNA sequencing data","volume":"20","author":"Abdelaal","year":"2019","journal-title":"Genome Biol."},{"volume-title":"Information Theory","year":"1965","author":"Ash","key":"2023040600413515800_"},{"key":"2023040600413515800_","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13059-016-0927-y","article-title":"Design and computational analysis of single-cell RNA-sequencing experiments","volume":"17","author":"Bacher","year":"2016","journal-title":"Genome Biol."},{"key":"2023040600413515800_","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1038\/nmeth.2645","article-title":"Accounting for technical noise in single-cell RNA-seq experiments","volume":"10","author":"Brennecke","year":"2013","journal-title":"Nat. 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