[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-329788-105":59,"doc-detail-329788-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","orchard-building-large-cancer-phylogenies-using-stochastic-combinatorial-search","Orchard - Building large cancer phylogenies using stochastic combinatorial search","","Cancer phylogenies reveal how genetically distinct cell subpopulations evolve within the same tumor and they can inform development understanding and treatment planning. Existing bulk-sequencing approaches often lose accuracy when more than 30 mutations are involved, and sometimes fail entirely. Orchard introduces a fast, accurate reconstruction method using stochastic combinatorial search up to 1,000 mutations by sequentially optimizing factors of a factorized posterior approximation.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/orchard-building-large-cancer-phylogenies-using-stochastic-combinatorial-search/329788/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/orchard-building-large-cancer-phylogenies-using-stochastic-combinatorial-search/329788.png","ImageObject",300,407,{"name":92,"@type":93},"Aurelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-13","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does Orchard address in reconstructing cancer phylogenies?","Question",{"text":112,"@type":113},"Orchard targets the inaccuracy or failure of existing reconstruction methods when handling cancer phylogenies with more than about 30 mutations.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does Orchard build large phylogenetic trees from sequencing data?",{"text":117,"@type":113},"It samples without replacement from a factorized approximation of the posterior over phylogenies and sequentially optimizes factors, growing incrementally larger trees until all mutations are included.",{"name":119,"@type":110,"acceptedAnswer":120},"What evidence is reported for Orchard’s performance and utility?",{"text":121,"@type":113},"Evaluations show improved reconstruction of plausible phylogenies across 90 simulated cancers and 14 B-progenitor acute lymphoblastic leukemias, including accurate results up to 1,000 mutations, and the reconstructed large trees help identify mutation patterns across subpopulations.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},329788,1790240783,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":31,"preview_page_count":4},1099514068365,"https://ap-avatar.wpscdn.com/avatar/10000253d8d9f28188e?x-image-process=image/resize,m_fixed,w_180,h_180&k=1794309523707217728","PLOS COMPUTATIONAL BIOLOGY  \nOPEN ACCESS  \nCitation: Kulman E, Kuang R, Morris Q (2024) Orchard: Building large cancer phylogenies using stochastic combinatorial search. PLoS Comput Biol 20(12): e1012653 . [https://doi.org/10.1371/journal](https://doi.org/10.1371/journal). pcbi.1012653  \nEditor: Mohammed El-Kebir, University of Illinois at Urbana-Champaign, UNITED STATES OF AMERICA  \nReceived: July 10, 2024  \nAccepted: November 18, 2024  \nPublished: December 30, 2024  \nCopyright: © 2024 Kulman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.  \nData Availability Statement: The Orchard source code is accessible under an MIT license at [https://](https://)[ ](https://)[github.com/morrislab/orchard](github.com/morrislab/orchard. Experiment data is)[. Experiment data is](github.com/morrislab/orchard. Experiment data is)[ ](github.com/morrislab/orchard. Experiment data is)available at [https://github.com/morrislab/orchard/](https://github.com/morrislab/orchard/)[ ](https://github.com/morrislab/orchard/)[tree/main/data](tree/main/data.)[.](tree/main/data.)  \nFunding: Q. M. was partially supported by a NIH/ NCI Cancer Center Support Grant P30 CA008748 (Vickers) . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.  \nCompeting interests: The authors have declared that no competing interests exist.  \nMETHODS  \nOrchard: Building large cancer phylogenies using stochastic combinatorial search  \nEthan Kulman1,2, Rui Kuang2, Quaid Morris1 *  \n1 Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America, 2 Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota, United States of America  \n* [MorrisQ@mskcc.org](MorrisQ@mskcc.org)  \nAbstract  \nPhylogenies depicting the evolutionary history of genetically heterogeneous subpopulations of cells from the same cancer, i.e. , cancer phylogenies, offer valuable insights about cancer development and guide treatment strategies. Many methods exist that reconstruct cancer phylogenies using point mutations detected with bulk DNA sequencing. However, these methods become inaccurate when reconstructing phylogenies with more than 30 mutations, or, in some cases, fail to recover a phylogeny altogether. Here, we introduce Orchard, a cancer phylogeny reconstruction algorithm that is fast and accurate using up to 1000 mutations. Orchard samples without replacement from a factorized approximation of the posterior distribution over phylogenies, a novel result derived in this paper. Each factor in this approximate posterior corresponds to a conditional distribution for adding a new mutation to a partially built phylogeny. Orchard optimizes each factor sequentially, generating a sequence of incrementally larger phylogenies that ultimately culminate in a complete tree containing all mutations. Our evaluations demonstrate that Orchard outperforms state-of-the-art cancer phylogeny reconstruction methods in reconstructing more plausible phylogenies across 90 simulated cancers and 14 B-progenitor acute lymphoblastic leukemias (B-ALLs) . Remarkably, Orchard accurately reconstructs cancer phylogenies using up to 1,000 mutations. Additionally, we demonstrate that the large and accurate phylogenies reconstructed by Orchard are useful for identifying patterns of somatic mutations and genetic variations among distinct cancer cell subpopulations.  \nAuthor summary  \nSomatic mutations accumulate during cancer progression, leading to genetically distinct subpopulations of cancer cells. Understanding the evolutionary relationships among these subpopulations reveals critical events and offers clinical insights for treatment. We developed a novel machine learning a","cbCaitKiryWOlme8","https://ap.wps.com/l/cbCaitKiryWOlme8","pdf",1760664,"English","# Methods\n## Orchard: Building large cancer phylogenies using stochastic combinatorial search\n# Abstract\n# Author summary\n# Introduction","[{\"question\":\"What problem does Orchard address in reconstructing cancer phylogenies?\",\"answer\":\"Orchard targets the inaccuracy or failure of existing reconstruction methods when handling cancer phylogenies with more than about 30 mutations.\"},{\"question\":\"How does Orchard build large phylogenetic trees from sequencing data?\",\"answer\":\"It samples without replacement from a factorized approximation of the posterior over phylogenies and sequentially optimizes factors, growing incrementally larger trees until all mutations are included.\"},{\"question\":\"What evidence is reported for Orchard’s performance and utility?\",\"answer\":\"Evaluations show improved reconstruction of plausible phylogenies across 90 simulated cancers and 14 B-progenitor acute lymphoblastic leukemias, including accurate results up to 1,000 mutations, and the reconstructed large trees help identify mutation patterns across subpopulations.\"}]","Orchard - Building large cancer phylogenies using stochastic combinatorial search | PDF",1789985628]