eng
Schloss Dagstuhl – Leibniz-Zentrum für Informatik
Leibniz International Proceedings in Informatics
1868-8969
2019-09-03
18:1
18:5
10.4230/LIPIcs.WABI.2019.18
article
Detecting Transcriptomic Structural Variants in Heterogeneous Contexts via the Multiple Compatible Arrangements Problem
Qiu, Yutong
1
Ma, Cong
1
Xie, Han
1
Kingsford, Carl
1
Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA
Transcriptomic structural variants (TSVs) - large-scale transcriptome sequence change due to structural variation - are common, especially in cancer. Detecting TSVs is a challenging computational problem. Sample heterogeneity (including differences between alleles in diploid organisms) is a critical confounding factor when identifying TSVs. To improve TSV detection in heterogeneous RNA-seq samples, we introduce the Multiple Compatible Arrangement Problem (MCAP), which seeks k genome rearrangements to maximize the number of reads that are concordant with at least one rearrangement. This directly models the situation of a heterogeneous or diploid sample. We prove that MCAP is NP-hard and provide a 1/4-approximation algorithm for k=1 and a 3/4-approximation algorithm for the diploid case (k=2) assuming an oracle for k=1. Combining these, we obtain a 3/16-approximation algorithm for MCAP when k=2 (without an oracle). We also present an integer linear programming formulation for general k. We characterize the graph structures that require k>1 to satisfy all edges and show such structures are prevalent in cancer samples. We evaluate our algorithms on 381 TCGA samples and 2 cancer cell lines and show improved performance compared to the state-of-the-art TSV-calling tool, SQUID.
https://drops.dagstuhl.de/storage/00lipics/lipics-vol143-wabi2019/LIPIcs.WABI.2019.18/LIPIcs.WABI.2019.18.pdf
transcriptomic structural variation
integer linear programming
heterogeneity