[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-331907-105":59,"doc-detail-331907-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","building-flexible-and-robust-analysis-frameworks-for-molecular-subtyping-of-cancers","Building flexible and robust analysis frameworks for molecular subtyping of cancers","","Molecular subtyping underpins inference of tumor aggressiveness and prognosis, yet clinical tumor profiling depends on in-depth bioinformatics expertise and can be hindered by data incompatibility across platforms (e.g., microarray versus RNA sequencing) and by technical or uncharacterized biological variance between training and test sets. The work proposes a roadmap for implementing clinical bioinformatics frameworks for human cancer molecular profiling. It integrates quality control, normalization, batch correction, classification and reporting, and demonstrates the framework through a breast cancer use case.",{"@graph":69,"@context":123},[70,84,106],{"@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/building-flexible-and-robust-analysis-frameworks-for-molecular-subtyping-of-cancers/331907/",{"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/building-flexible-and-robust-analysis-frameworks-for-molecular-subtyping-of-cancers/331907.png","ImageObject",300,407,{"name":92,"@type":93},"Anda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-05","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is molecular subtyping important in cancer care?","Question",{"text":113,"@type":114},"Molecular subtyping helps infer tumor aggressiveness and predict prognosis, supporting patient stratification in precision medicine.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What challenges affect molecular subtyping in diagnostic laboratories?",{"text":118,"@type":114},"Clinical profiling can be affected by small sample sizes, batch-dependent differences, tumor purity effects, and incompatibility between microarray-derived methods and RNA-sequencing-based gene expression profiling.",{"name":120,"@type":111,"acceptedAnswer":121},"What does the proposed framework include?",{"text":122,"@type":114},"The framework integrates quality control, normalization, batch correction, classification, and reporting, and includes a breast cancer use case.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},331907,1791161615,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},962075006959,"https://ap-avatar.wpscdn.com/avatar/e0002397efbe92a78e?_k=1776741047341049297","Building flexible and robust analysis frameworks for molecular subtyping of cancers  \nChristina Bligaard Pedersen 1,2, Benito Campos 1, Lasse Rene 1, Helene Scheel Wegener 1, Neeraja M. Krishnan3, Binay Panda 1,3,4, Kristoffer Vitting-Seerup 1, Maria Rossing2, Frederik Otzen Bagger2 and Lars Rønn Olsen 1   \n1 Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark  \n2 Center for Genomic Medicine, Rigshospitalet – Copenhagen University Hospital, Denmark  \n3 School of Biotechnology, Jawaharlal Nehru University, New Delhi, India  \n4 Special Centre for Systems Medicine, Jawaharlal Nehru University, New Delhi, India  \nKeywords  \nbioinformatics workflows; clinical bioinformatics; molecular subtyping; sample classification  \nCorrespondence  \nL. R. Olsen, Department of Health Technology, Technical University of Denmark, Anker Engelunds Vej 1, 2800 Kongens Lyngby, Denmark  \nE-mail: [lronn@dtu.dk](lronn@dtu.dk)  \n(Received 7 June 2023, revised 19 October 2023, accepted 28 December 2023, available online 7 January 2024)  \ndoi:10 . 1002/1878-0261 .13580  \nMolecular subtyping is essential to infer tumor aggressiveness and predict prognosis. In practice, tumor profiling requires in-depth knowledge of bioinformatics tools involved in the processing and analysis of the generated data. Additionally, data incompatibility (e.g., microarray versus RNA sequencing data) and technical and uncharacterized biological variance between training and test data can pose challenges in classifying individual samples. In this article, we provide a roadmap for implementing bioinformatics frameworks for molecular profiling of human cancers in a clinical diagnostic setting. We describe a framework for integrating several methods for quality control, normalization, batch correction, classification and reporting, and develop a use case of the framework in breast cancer.  \n1. Introduction  \nLarge-scale multi-omics profiling experiments during the last decade have defined tumor subtypes in glioblastoma, breast cancer, squamous cell lung cancer, and colorectal cancer [1–4] . Morphologically similar tumor samples can differ substantially in underlying genetic aberrations and changes in gene expression. For several cancers, specific tumor subtypes have been linked to different treatment responses and prognoses [5–7],  \nproviding an important approach for patient stratification and its application in precision medicine.  \nIn the case of breast cancer, the definition of subtypes has a history extending two decades [8–10] and tumor profiling is already integrated into many modern clinical workflows [11] . More than 100 expression profiles have been proposed [12], however, in practice, the most widely used subtyping methods are the PAM50 [9] and CIT [10] gene signatures. PAM50 is used to classify samples into one of four subtypes:  \nAbbreviations  \nBasL, basal-like; BRCA, breast invasive carcinoma; CIT, Cartes d’Identit des Tumeurs program; CITBCMST, CIT breast cancer molecular subtypes prediction; EGA, European genome-phenome archive; ER, estrogen receptor; ERBB2, receptor tyrosine-protein kinase erbB-2; ESR1, estrogen receptor 1; FDA, Food and Drug Administration; FISH, fluorescence in situ hybridization; GTEx, genotype-tissue expression; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; kNN, k nearest neighbors; LumA, luminal A; LumB, luminal B; LumC, luminal C; mApo, molecular-apocrine; NormL, normal-like; PAM50, Prediction Analysis of Microarray 50; PCA, principal component analysis; PCs, principal components; PR, progesterone receptor; qRT-PCR, quantitative reverse transcription polymerase chain reaction; RMA, robust multi-array average; RSEM, RNA-Seq by expectation–maximization; ssGSEA, single-sample gene set enrichment analysis; SVA, surrogate variable analysis; TCGA, The cancer genome atlas; TPM, transcripts per million.  \n606 Molecular Oncology 18 (2024) 606–619 ª 2023 The Authors. Molecular Oncology published by John W","cbCaik15TSFFTBx9","https://ap.wps.com/l/cbCaik15TSFFTBx9","pdf",1844068,14,"English","# Introduction\n## Molecular subtyping rationale\n## Challenges in clinical sample classification\n## Framework roadmap for clinical profiling","[{\"question\":\"Why is molecular subtyping important in cancer care?\",\"answer\":\"Molecular subtyping helps infer tumor aggressiveness and predict prognosis, supporting patient stratification in precision medicine.\"},{\"question\":\"What challenges affect molecular subtyping in diagnostic laboratories?\",\"answer\":\"Clinical profiling can be affected by small sample sizes, batch-dependent differences, tumor purity effects, and incompatibility between microarray-derived methods and RNA-sequencing-based gene expression profiling.\"},{\"question\":\"What does the proposed framework include?\",\"answer\":\"The framework integrates quality control, normalization, batch correction, classification, and reporting, and includes a breast cancer use case.\"}]","Building flexible and robust analysis frameworks for molecular subtyping of cancers | PDF",1789995708,35]