期刊名称：Computational and Structural Biotechnology Journal
印刷版ISSN：2001-0370
出版年度：2020
卷号：18
页码：1664-1675
DOI：10.1016/j.csbj.2020.06.022
出版社：Computational and Structural Biotechnology Journal
摘要：In cancer, recurrently mutated sites in DNA and proteins, called hotspots , are thought to be raised by positive selection and therefore important due to its potential functional impact. Although recent evidence for APOBEC enzymatic activity have shown that specific types of sequences are likely to be false, the identification of putative hotspots is important to confirm either its functional role or its mechanistic bias. In this work, an algorithm and a statistical model is presented to detect hotspots. The model consists of a beta-binomial component plus fixed effects that efficiently fits the distribution of mutated sites. The algorithm employs an optimal stepwise approach to find the model parameters. Simulations show that the proposed algorithmic model is highly accurate for common hotspots. The approach has been applied to TCGA mutational data from 33 cancer types. The results show that well-known cancer hotspots are easily detected. Besides, novel hotspots are also detected. An analysis of the sequence context of detected hotspots show a preference for TCG sites that may be related to APOBEC or other unknown mechanistic biases. The detected hotspots are available online in http://bioinformatica.mty.itesm.mx/HotSpotsAnnotations .
