DeePaN: deep patient graph convolutional network integrating clinico-genomic evidence to stratify lung cancers for immunotherapy

Abstract Immuno-oncology (IO) therapies have transformed the therapeutic landscape of non-small cell lung cancer (NSCLC). However, patient responses to IO are variable and influenced by a heterogeneous combination of health, immune, and tumor factors. There is a pressing need to discover the distinc...

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Autores principales:	Chao Fang, Dong Xu, Jing Su, Jonathan R Dry, Bolan Linghu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Computer applications to medicine. Medical informatics R858-859.7
Acceso en línea:	https://doaj.org/article/99ccbd25da274e779adb31be74a930d9
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spelling	oai:doaj.org-article:99ccbd25da274e779adb31be74a930d92021-12-02T14:40:03ZDeePaN: deep patient graph convolutional network integrating clinico-genomic evidence to stratify lung cancers for immunotherapy10.1038/s41746-021-00381-z2398-6352https://doaj.org/article/99ccbd25da274e779adb31be74a930d92021-02-01T00:00:00Zhttps://doi.org/10.1038/s41746-021-00381-zhttps://doaj.org/toc/2398-6352Abstract Immuno-oncology (IO) therapies have transformed the therapeutic landscape of non-small cell lung cancer (NSCLC). However, patient responses to IO are variable and influenced by a heterogeneous combination of health, immune, and tumor factors. There is a pressing need to discover the distinct NSCLC subgroups that influence response. We have developed a deep patient graph convolutional network, we call “DeePaN”, to discover NSCLC complexity across data modalities impacting IO benefit. DeePaN employs high-dimensional data derived from both real-world evidence (RWE)-based electronic health records (EHRs) and genomics across 1937 IO-treated NSCLC patients. DeePaN demonstrated effectiveness to stratify patients into subgroups with significantly different (P-value of 2.2 × 10−11) overall median survival of 20.35 months and 9.42 months post-IO therapy. Significant differences in IO outcome were not seen from multiple non-graph-based unsupervised methods. Furthermore, we demonstrate that patient stratification from DeePaN has the potential to augment the emerging IO biomarker of tumor mutation burden (TMB). Characterization of the subgroups discovered by DeePaN indicates potential to inform IO therapeutic insight, including the enrichment of mutated KRAS and high blood monocyte count in the IO beneficial and IO non-beneficial subgroups, respectively. Our work has proven the concept that graph-based AI is feasible and can effectively integrate high-dimensional genomic and EHR data to meaningfully stratify cancer patients on distinct clinical outcomes, with potential to inform precision oncology.Chao FangDong XuJing SuJonathan R DryBolan LinghuNature PortfolioarticleComputer applications to medicine. Medical informaticsR858-859.7ENnpj Digital Medicine, Vol 4, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Computer applications to medicine. Medical informatics R858-859.7
spellingShingle	Computer applications to medicine. Medical informatics R858-859.7 Chao Fang Dong Xu Jing Su Jonathan R Dry Bolan Linghu DeePaN: deep patient graph convolutional network integrating clinico-genomic evidence to stratify lung cancers for immunotherapy
description	Abstract Immuno-oncology (IO) therapies have transformed the therapeutic landscape of non-small cell lung cancer (NSCLC). However, patient responses to IO are variable and influenced by a heterogeneous combination of health, immune, and tumor factors. There is a pressing need to discover the distinct NSCLC subgroups that influence response. We have developed a deep patient graph convolutional network, we call “DeePaN”, to discover NSCLC complexity across data modalities impacting IO benefit. DeePaN employs high-dimensional data derived from both real-world evidence (RWE)-based electronic health records (EHRs) and genomics across 1937 IO-treated NSCLC patients. DeePaN demonstrated effectiveness to stratify patients into subgroups with significantly different (P-value of 2.2 × 10−11) overall median survival of 20.35 months and 9.42 months post-IO therapy. Significant differences in IO outcome were not seen from multiple non-graph-based unsupervised methods. Furthermore, we demonstrate that patient stratification from DeePaN has the potential to augment the emerging IO biomarker of tumor mutation burden (TMB). Characterization of the subgroups discovered by DeePaN indicates potential to inform IO therapeutic insight, including the enrichment of mutated KRAS and high blood monocyte count in the IO beneficial and IO non-beneficial subgroups, respectively. Our work has proven the concept that graph-based AI is feasible and can effectively integrate high-dimensional genomic and EHR data to meaningfully stratify cancer patients on distinct clinical outcomes, with potential to inform precision oncology.
format	article
author	Chao Fang Dong Xu Jing Su Jonathan R Dry Bolan Linghu
author_facet	Chao Fang Dong Xu Jing Su Jonathan R Dry Bolan Linghu
author_sort	Chao Fang
title	DeePaN: deep patient graph convolutional network integrating clinico-genomic evidence to stratify lung cancers for immunotherapy
title_short	DeePaN: deep patient graph convolutional network integrating clinico-genomic evidence to stratify lung cancers for immunotherapy
title_full	DeePaN: deep patient graph convolutional network integrating clinico-genomic evidence to stratify lung cancers for immunotherapy
title_fullStr	DeePaN: deep patient graph convolutional network integrating clinico-genomic evidence to stratify lung cancers for immunotherapy
title_full_unstemmed	DeePaN: deep patient graph convolutional network integrating clinico-genomic evidence to stratify lung cancers for immunotherapy
title_sort	deepan: deep patient graph convolutional network integrating clinico-genomic evidence to stratify lung cancers for immunotherapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/99ccbd25da274e779adb31be74a930d9
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DeePaN: deep patient graph convolutional network integrating clinico-genomic evidence to stratify lung cancers for immunotherapy

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