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Title: PLUS: Predicting cancer metastasis potential based on positive and unlabeled learning
Metastatic cancer accounts for over 90% of all cancer deaths, and evaluations of metastasis potential are vital for minimizing the metastasis-associated mortality and achieving optimal clinical decision-making. Computational assessment of metastasis potential based on large-scale transcriptomic cancer data is challenging because metastasis events are not always clinically detectable. The under-diagnosis of metastasis events results in biased classification labels, and classification tools using biased labels may lead to inaccurate estimations of metastasis potential. This issue is further complicated by the unknown metastasis prevalence at the population level, the small number of confirmed metastasis cases, and the high dimensionality of the candidate molecular features. Our proposed algorithm, called P ositive and unlabeled L earning from U nbalanced cases and S parse structures ( PLUS ), is the first to use a positive and unlabeled learning framework to account for the under-detection of metastasis events in building a classifier. PLUS is specifically tailored for studying metastasis that deals with the unbalanced instance allocation as well as unknown metastasis prevalence, which are not considered by other methods. PLUS achieves superior performance on synthetic datasets compared with other state-of-the-art methods. Application of PLUS to The Cancer Genome Atlas Pan-Cancer gene expression data generated metastasis potential predictions that show good agreement with the clinical follow-up data, in addition to predictive genes that have been validated by independent single-cell RNA-sequencing datasets.  more » « less
Award ID(s):
2047631 1850360 2528521
PAR ID:
10320023
Author(s) / Creator(s):
; ; ; ; ; ;
Editor(s):
Liu, Jie
Date Published:
Journal Name:
PLOS Computational Biology
Volume:
18
Issue:
3
ISSN:
1553-7358
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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