{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T21:02:33Z","timestamp":1776459753746,"version":"3.51.2"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"Supplement_2","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["NSF 2238125"],"award-info":[{"award-number":["NSF 2238125"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HG 009299-6A1"],"award-info":[{"award-number":["R01 HG 009299-6A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 EY 030546-01A1"],"award-info":[{"award-number":["R01 EY 030546-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Understanding causal effects is a fundamental goal of science and underpins our ability to make accurate predictions in unseen settings and conditions. While direct experimentation is the gold standard for measuring and validating causal effects, the field of causal graph theory offers a tantalizing alternative: extracting causal insights from observational data. Theoretical analysis has shown that this is indeed possible, given a large dataset and if certain conditions are met. However, biological datasets, frequently, do not meet such requirements but evaluation of causal discovery algorithms is typically performed on synthetic datasets, which they meet all requirements. Thus, real-life datasets are needed, in which the causal truth is reasonably known. In this work we first construct such a large-scale real-life dataset and then we perform on it a comprehensive benchmarking of various causal discovery methods.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We find that the PC algorithm is particularly accurate at estimating causal structure, including the causal direction which is critical for biological applicability. However, PC does only produces cause-effect directionality, but not estimates of causal effects. We propose PC-NOTEARS (PCnt), a hybrid solution, which includes the PC output as an additional constraint inside the NOTEARS optimization. This approach combines PC algorithm\u2019s strengths in graph structure prediction with the NOTEARS continuous optimization to estimate causal effects accurately. PCnt achieved best aggregate performance across all structural and effect size metrics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>https:\/\/github.com\/zhu-yh1\/PC-NOTEARS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae411","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T07:33:39Z","timestamp":1725521619000},"page":"ii87-ii97","source":"Crossref","is-referenced-by-count":6,"title":["A hybrid constrained continuous optimization approach for optimal causal discovery from biological data"],"prefix":"10.1093","volume":"40","author":[{"given":"Yuehua","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Computational and Systems Biology, University of Pittsburgh , Pittsburgh, PA 15217, United States"},{"name":"School of Medicine, Tsinghua University , Beijing 100084, 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