[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-detail-122903-en":3,"doc-seo-122903-105":30,"detail-sidebar-cat-0-en-105":91},{"code":4,"msg":5,"data":6},0,"success",{"doc_id":7,"user_id":8,"nickname":9,"user_avatar":10,"doc_module":4,"category_id":11,"category_name":12,"doc_title":13,"doc_description":14,"doc_content":15,"file_id":16,"file_url":17,"file_type":18,"file_size":19,"view_count":4,"is_deleted":4,"is_public":20,"is_downloadable":20,"audit_status":20,"page_count":21,"language":22,"language_code":23,"site_id":24,"html_lang":23,"table_of_contents":25,"faqs":26,"seo_title":27,"seo_description":14,"update_tm":28,"read_time":29},122903,137441390410,"Hazel","https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984",8,"Research & Report","Machine learning dissection of Human Accelerated Regions in primate neurodevelopment","Machine learning interrogated the function of all human–chimpanzee variants across 2,645 Human Accelerated Regions (HARs), identifying 43% with variants showing large opposing chromatin-state effects and 14% affecting neurodevelopmental enhancer activity. The pattern supported compensatory evolution and was validated with massively parallel reporter assays in chimpanzee and human neural progenitor cells. Species-specific enhancer activity was predicted from transcription-factor footprints, while HAR sequences displayed nearly identical cis activity between species, implying HAR evolution targeted binding capacity rather than trans-environment compensation.","UCSF  \nUC San Francisco Previously Published Works  \nTitle  \nMachine learning dissection of human accelerated regions in primate neurodevelopment.  \nPermalink  \n[https://escholarship.org/uc/item/45j3b4vn](https://escholarship.org/uc/item/45j3b4vn)  \nJournal  \nNeuron, 111(6)  \nAuthors  \nWhalen, Sean  \nInoue, Fumitaka Ryu, Haneet al.  \nPublication Date  \n2023-03-15  \nDOI  \n10.1016/j. neuron.2022.12.026  \nPeer reviewed  \n[eScholarship.org](eScholarship.org) Powered by the California Digital Library  \nUniversity of California  \nAuthor Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript  \n\n|  | HHS Public Access\u003Cbr>Author manuscript\u003Cbr>Neuron. Author manuscript; available in PMC 2024 March 15. |\n| --- | --- |\n\nPublished in final edited form as:  \nNeuron. 2023 March 15; 111(6): 857–873.e8. doi:10.1016/j.neuron.2022.12.026 .  \nMachine learning dissection of Human Accelerated Regions in primate neurodevelopment  \nSean Whalen 1,^ , Fumitaka Inoue2,3,4,^ , Hane Ryu2,3,5,^ , Tyler Fairr6,7 , Eirene MarkenscoffPapadimitriou8 , Kathleen Keough 1,5 , Martin Kircher9,10,11 , Beth Martin9 , Beatriz Alvarado6 , Orry Elor2,3 , Dianne Laboy Cintron2,3 , Alex Williams 1 , Md. Abul Hassan Samee 1 , Sean Thomas 1 , Robert Krencik 12 , Erik M. Ullian 13,14 , Arnold Kriegstein6,7 , John L. Rubenstein8 , Jay Shendure9,15,16 , Alex A. Pollen3,6,7 , Nadav Ahituv2,3,* , Katherine S. Pollard 1,3,17,18,*,$  \n1Gladstone Institutes, San Francisco, CA 94158, USA  \n2 Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA  \n3 Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA  \n4 Present address: Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan  \n5 Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California San Francisco, San Francisco, CA, USA  \n6 Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143  \n7 Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA  \n8 Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA  \n9 Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA  \n10Berlin Institute of Health at Charité–Universitätsmedizin Berlin, 10117 Berlin, Germany  \n11 Institute of Human Genetics, University Medical Center Schleswig-Holstein, University of Lübeck, 23562 Lübeck, Germany  \n*[Correspondence: katherine.pollard@gladstone.ucsf.edu](Correspondence: katherine.pollard@gladstone.ucsf.edu) (K. S.P.), [nadav.ahituv@ucsf.edu](nadav.ahituv@ucsf.edu) (N.A.) .  \nAuthor Contributions  \nS.W., H.R., F.I., N.A., and K.S.P. conceived and designed the study. S.W., A.W., S.T., and K.S.P. designed the lentiMPRA library.  \nS.W., K.K., M.K., M.A.H.S., and K.S.P. analyzed data and performed modeling. F.I., H.R., T.F., A.A.P., E.M.P., B.M., B.A., O.E., D.L.C., and R.K. performed experiments. S.W., F.I., H.R., E.M.P., J.S., A.A.P., N.A., and K.S.P. interpreted results. E.U., J.L.R., A.R.K., J.S., A.A.P., N.A., and K.S.P. supervised and provided funding. S.W. and K.S.P. drafted the manuscript. All authors reviewed and edited the manuscript.  \n^These authors contributed equally to the work.  \n$[Lead contact: katherine.pollard@gladstone.ucsf.edu](Lead contact: katherine.pollard@gladstone.ucsf.edu) (K. S.P.)  \nPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.  \nAuthor Manuscr i","cbCailJGLnDqwlMA","https://ap.wps.com/l/cbCailJGLnDqwlMA","pdf",2336075,1,43,"English","en",105,"# Summary\n## Study approach using machine learning\n## Validation with reporter assays\n## Predictions from transcription-factor footprints\n## Interpretation of cis activity differences","[{\"question\":\"What did the machine learning model analyze in human accelerated regions (HARs)?\",\"answer\":\"It interrogated the function of all human–chimpanzee variants across 2,645 HARs, focusing on effects on chromatin state and neurodevelopmental enhancer activity.\"},{\"question\":\"How were the ML findings validated experimentally?\",\"answer\":\"The pattern was confirmed using massively parallel reporter assays in chimpanzee and human neural progenitor cells.\"},{\"question\":\"What does the similar cis activity in human and chimpanzee cells suggest about HAR evolution?\",\"answer\":\"It suggests HARs did not primarily evolve to compensate for trans-environment changes; instead, they likely altered their ability to bind factors present in both species.\"}]","Machine learning dissection of Human Accelerated Regions in primate neurodevelopment | PDF",1785813579,108,{"code":4,"msg":31,"data":32},"ok",{"site_id":24,"language":23,"slug":33,"title":13,"keywords":34,"description":14,"schema_data":35,"social_meta":86,"head_meta":88,"extra_data":90,"updated_unix":28},"machine-learning-dissection-of-human-accelerated-regions-in-primate-neurodevelopment","",{"@graph":36,"@context":85},[37,54,68],{"@type":38,"itemListElement":39},"BreadcrumbList",[40,44,48,51],{"item":41,"name":42,"@type":43,"position":20},"https://docshare.wps.com","Home","ListItem",{"item":45,"name":46,"@type":43,"position":47},"https://docshare.wps.com/document/","Document",2,{"item":49,"name":12,"@type":43,"position":50},"https://docshare.wps.com/document/research-report/",3,{"item":52,"name":13,"@type":43,"position":53},"https://docshare.wps.com/document/machine-learning-dissection-of-human-accelerated-regions-in-primate-neurodevelopment/122903/",4,{"url":52,"name":13,"@type":55,"author":56,"headline":13,"publisher":58,"fileFormat":61,"inLanguage":23,"description":14,"dateModified":62,"datePublished":62,"encodingFormat":61,"isAccessibleForFree":63,"interactionStatistic":64},"DigitalDocument",{"name":9,"@type":57},"Person",{"url":41,"name":59,"@type":60},"DocShare","Organization","application/pdf","2026-08-04",true,{"@type":65,"interactionType":66,"userInteractionCount":4},"InteractionCounter",{"@type":67},"ViewAction",{"@type":69,"mainEntity":70},"FAQPage",[71,77,81],{"name":72,"@type":73,"acceptedAnswer":74},"What did the machine learning model analyze in human accelerated regions (HARs)?","Question",{"text":75,"@type":76},"It interrogated the function of all human–chimpanzee variants across 2,645 HARs, focusing on effects on chromatin state and neurodevelopmental enhancer activity.","Answer",{"name":78,"@type":73,"acceptedAnswer":79},"How were the ML findings validated experimentally?",{"text":80,"@type":76},"The pattern was confirmed using massively parallel reporter assays in chimpanzee and human neural progenitor cells.",{"name":82,"@type":73,"acceptedAnswer":83},"What does the similar cis activity in human and chimpanzee cells suggest about HAR evolution?",{"text":84,"@type":76},"It suggests HARs did not primarily evolve to compensate for trans-environment changes; 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