Inferring Sequential Order of Somatic Mutations during Tumorgenesis based on Markov Chain Model

PROJECT TITLE :

Inferring Sequential Order of Somatic Mutations during Tumorgenesis based on Markov Chain Model

ABSTRACT:

Tumors are developed and worsen with the accumulated mutations on DNA sequences throughout tumorigenesis. Identifying the temporal order of gene mutations in cancer initiation and development could be a challenging topic. It not solely provides a brand new insight into the study of tumorigenesis at the level of genome sequences however also is a good tool for early diagnosis of tumors and preventive drugs. In this paper, we develop a novel method to accurately estimate the sequential order of gene mutations throughout tumorigenesis from genome sequencing data primarily based on Markov chain model as TOMC (Temporal Order based mostly on Markov Chain), and additionally provide a new criterion to additional infer the order of samples or patients, which will characterize the severity or stage of the disease. We have a tendency to applied our method to the analysis of tumors based on many high-throughput datasets. Specifically, 1st, we tend to revealed that tumor suppressor genes (TSG) have a tendency to be mutated earlier than oncogenes, which are considered as necessary events for key useful loss and gain throughout tumorigenesis. Second, the comparisons of numerous ways demonstrated that our approach has clear benefits over the prevailing ways thanks to the thought on the impact of mutation dependence among genes, like co-mutation. Third and most vital, our method is in a position to deduce the ordinal sequence of patients or samples to quantitatively characterize their severity of tumors. Thus, our work provides a brand new manner to quantitatively understand the event and progression of tumorigenesis based mostly on high throughput sequencing data.

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