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iSeg: an efficient algorithm for segmentation of genomic and epigenomic data

By S.B. Girimurugan, Yuhang Liu, Pei-Yau Lung, Daniel L. Vera, Jonathan H. Dennis, Hank W. Bass, Jinfeng Zhang

Posted 05 Sep 2017
bioRxiv DOI: 10.1101/184515 (published DOI: 10.1186/s12859-018-2140-3)

Background: Identification of functional elements of a genome often requires dividing a sequence of measurements along a genome into segments where adjacent segments have different properties, such as different mean values. This problem is often called the segmentation problem in the field of genomics, and the change-point problem in other scientific disciplines. Despite dozens of algorithms developed to address this problem in genomics research, methods with improved accuracy and speed are still needed to effectively tackle both existing and emerging genomic and epigenomic segmentation problems. Results: We designed an efficient algorithm, called iSeg, for segmentation of genomic and epigenomic profiles. iSeg first utilizes dynamic programming to identify candidate segments and test for significance. It then uses a novel data structure based on two coupled balanced binary trees to detect overlapping significant segments and update them simultaneously during searching and refinement stages. Refinement and merging of significant segments are performed at the end to generate the final set of segments. By using an objective function based on the p-values of the segments, the algorithm can serve as a general computational framework to be combined with different assumptions on the distributions of the data. As a general segmentation method, it can segment different types of genomic and epigenomic data, such as DNA copy number variation, nucleosome occupancy, nuclease sensitivity, and differential nuclease sensitivity data. Using simple t-tests to compute p-values across multiple datasets of different types, we evaluate iSeg using both simulated and experimental datasets and show that it performs satisfactorily when compared with some state-of-art procedures, which often employ more sophisticated statistical models. Implemented in C++, iSeg is also computationally efficient, and well suited for large numbers of input profiles and data with very long sequences. Conclusions: We have developed an effective and efficient general-purpose segmentation tool for sequential data and illustrated its use in segmentation of genomic and epigenomic profiles.

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