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CUP-AI-Dx: A tool for inferring cancer tissue of origin and molecular subtype using RNA gene-expression data and artificial intelligence

التفاصيل البيبلوغرافية
العنوان: CUP-AI-Dx: A tool for inferring cancer tissue of origin and molecular subtype using RNA gene-expression data and artificial intelligence
المؤلفون: Yue Zhao, Ziwei Pan, Sandeep Namburi, Andrew Pattison, Atara Posner, Shiva Balachander, Carolyn A. Paisie, Honey V Reddi, Jens Rueter, Anthony J Gill, Stephen Fox, Kanwal P.S. Raghav, William F Flynn, Richard W. Tothill, Sheng Li, R. Krishna Murthy Karuturi, Joshy George
المصدر: EBioMedicine, Vol 61, Iss , Pp 103030- (2020)
بيانات النشر: Elsevier, 2020.
سنة النشر: 2020
المجموعة: LCC:Medicine
LCC:Medicine (General)
مصطلحات موضوعية: Cancer, TCGA, Classification, Machine learning, Deep learning, Cell-of-origin, Medicine, Medicine (General), R5-920
الوصف: Background: Cancer of unknown primary (CUP), representing approximately 3-5% of all malignancies, is defined as metastatic cancer where a primary site of origin cannot be found despite a standard diagnostic workup. Because knowledge of a patient's primary cancer remains fundamental to their treatment, CUP patients are significantly disadvantaged and most have a poor survival outcome. Developing robust and accessible diagnostic methods for resolving cancer tissue of origin, therefore, has significant value for CUP patients. Methods: We developed an RNA-based classifier called CUP-AI-Dx that utilizes a 1D Inception convolutional neural network (1D-Inception) model to infer a tumor's primary tissue of origin. CUP-AI-Dx was trained using the transcriptional profiles of 18,217 primary tumours representing 32 cancer types from The Cancer Genome Atlas project (TCGA) and International Cancer Genome Consortium (ICGC). Gene expression data was ordered by gene chromosomal coordinates as input to the 1D-CNN model, and the model utilizes multiple convolutional kernels with different configurations simultaneously to improve generality. The model was optimized through extensive hyperparameter tuning, including different max-pooling layers and dropout settings. For 11 tumour types, we also developed a random forest model that can classify the tumour's molecular subtype according to prior TCGA studies. The optimised CUP-AI-Dx tissue of origin classifier was tested on 394 metastatic samples from 11 tumour types from TCGA and 92 formalin-fixed paraffin-embedded (FFPE) samples representing 18 cancer types from two clinical laboratories. The CUP-AI-Dx molecular subtype was also independently tested on independent ovarian and breast cancer microarray datasets Findings: CUP-AI-Dx identifies the primary site with an overall top-1-accuracy of 98.54% in cross-validation and 96.70% on a test dataset. When applied to two independent clinical-grade RNA-seq datasets generated from two different institutes from the US and Australia, our model predicted the primary site with a top-1-accuracy of 86.96% and 72.46% respectively. Interpretation: The CUP-AI-Dx predicts tumour primary site and molecular subtype with high accuracy and therefore can be used to assist the diagnostic work-up of cancers of unknown primary or uncertain origin using a common and accessible genomics platform. Funding: NIH R35 GM133562, NCI P30 CA034196, Victorian Cancer Agency Australia.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2352-3964
Relation: http://www.sciencedirect.com/science/article/pii/S2352396420304060; https://doaj.org/toc/2352-3964
DOI: 10.1016/j.ebiom.2020.103030
URL الوصول: https://doaj.org/article/2e9c24dab6e948a488ab77e4c14eacf9
رقم الأكسشن: edsdoj.2e9c24dab6e948a488ab77e4c14eacf9
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23523964
DOI:10.1016/j.ebiom.2020.103030