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- W2599681060 abstract "Tumorigenesis is considered as a complex process that is often driven by close interactions between germline variants and accumulated somatic mutational events. Recent studies report that some somatic copy-number alternations show such interactions by harboring germline susceptibility variants under potential selection in clonal expansions. Incorporating these interactions into genetic association approach could be valuable in not only discovering novel susceptibility variants, but providing insight into tumor heterogeneity and clinical implications. To address this need, in this article, we propose RareProb-G, an expanded version of a computational method, which is designed for identifying rare germline susceptibility variants located in the somatic allelic amplification or loss of heterozygosity regions. RareProb-G is based on a hidden Markov random field model. The interactions among germline variants and somatic events are modeled by a neighborhood system, which is bounded by a t-test on variant allelic frequencies. Each variant is assigned four hidden states, which represent the regional status and causal/neutral status, respectively. A hidden Markov model is also introduced to estimate the initial values of the hidden states and unknown model parameters. To verify this approach, we conduct a series of simulation experiments under different configurations, and RareProb-G outperforms than RareProb on both sensitivity and specificity." @default.
- W2599681060 created "2017-04-07" @default.
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- W2599681060 date "2017-01-01" @default.
- W2599681060 modified "2023-09-24" @default.
- W2599681060 title "An Expanded Association Approach for Rare Germline Variants with Copy-Number Alternation" @default.
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- W2599681060 doi "https://doi.org/10.1007/978-3-319-56154-7_9" @default.
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