{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T14:42:28Z","timestamp":1775918548468,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21CA216452"],"award-info":[{"award-number":["R21CA216452"]}],"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":["R01HG010589"],"award-info":[{"award-number":["R01HG010589"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004897","name":"Pennsylvania Department of Health","doi-asserted-by":"publisher","award":["4100070287"],"award-info":[{"award-number":["4100070287"]}],"id":[{"id":"10.13039\/100004897","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mario Lemieux Foundation"},{"DOI":"10.13039\/100001513","name":"Breast Cancer Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001513","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AWS Machine Learning Research Awards"},{"name":"Center for Machine Learning and Health Fellowship"},{"DOI":"10.13039\/100004897","name":"The Pennsylvania Department of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004897","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>Identifying cell types and their abundances and how these evolve during tumor progression is critical to understanding the mechanisms of metastasis and identifying predictors of metastatic potential that can guide the development of new diagnostics or therapeutics. Single-cell RNA sequencing (scRNA-seq) has been especially promising in resolving heterogeneity of expression programs at the single-cell level, but is not always feasible, e.g. for large cohort studies or longitudinal analysis of archived samples. In such cases, clonal subpopulations may still be inferred via genomic deconvolution, but deconvolution methods have limited ability to resolve fine clonal structure and may require reference cell type profiles that are missing or imprecise. Prior methods can eliminate the need for reference profiles but show unstable performance when few bulk samples are available.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this work, we develop a new method using reference scRNA-seq to interpret sample collections for which only bulk RNA-seq is available for some samples, e.g. clonally resolving archived primary tissues using scRNA-seq from metastases. By integrating such information in a Quadratic Programming framework, our method can recover more accurate cell types and corresponding cell type abundances in bulk samples. Application to a breast tumor bone metastases dataset confirms the power of scRNA-seq data to improve cell type inference and quantification in same-patient bulk samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>Source code is available on Github at https:\/\/github.com\/CMUSchwartzLab\/RADs.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btac262","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T19:20:39Z","timestamp":1650050439000},"page":"i386-i394","source":"Crossref","is-referenced-by-count":8,"title":["Semi-deconvolution of bulk and single-cell RNA-seq data with application to metastatic progression in breast cancer"],"prefix":"10.1093","volume":"38","author":[{"given":"Haoyun","family":"Lei","sequence":"first","affiliation":[{"name":"Computational Biology Department, Carnegie Mellon University , Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan A","family":"Guo","sequence":"additional","affiliation":[{"name":"Computational Biology Department, Carnegie Mellon University , Pittsburgh, PA 15213, USA"},{"name":"Department of Biological Sciences, Carnegie Mellon University , Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifeng","family":"Tao","sequence":"additional","affiliation":[{"name":"Computational Biology Department, Carnegie Mellon University , Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, Magee-Womens Research Institute , Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuecong","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Carnegie Mellon University , Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffi","family":"Oesterreich","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, Magee-Womens Research Institute , Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian V","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, Magee-Womens Research Institute , Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4970-2252","authenticated-orcid":false,"given":"Russell","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Computational Biology Department, Carnegie Mellon University , Pittsburgh, PA 15213, USA"},{"name":"Department of Biological Sciences, Carnegie Mellon University , Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"2023041407561869900_","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.3390\/cancers12071765","article-title":"The CCL5\/CCR5 axis in cancer progression","volume":"12","author":"Aldinucci","year":"2020","journal-title":"Cancers (Basel)"},{"key":"2023041407561869900_","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1093\/bioinformatics\/bty1044","article-title":"M3Drop: dropout-based feature selection for scRNASeq","volume":"35","author":"Andrews","year":"2019","journal-title":"Bioinformatics"},{"key":"2023041407561869900_","doi-asserted-by":"crossref","first-page":"5650","DOI":"10.1038\/s41467-020-19015-1","article-title":"Benchmarking of cell type deconvolution pipelines for transcriptomics data","volume":"11","author":"Avila Cobos","year":"2020","journal-title":"Nat. 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