Authors and Affiliations

Authors and Affiliations

Jongkeun Lee^1,†, Andy Jinseok Lee^1,†, June-Koo Lee^2,†, Jongkeun Park¹, Youngoh Kwon¹, Seongyeol Park², Hyonho Chun³, Young Seok Ju^2,*,‡ and Dongwan Hong<sup>1,*,‡

1</sup>Clinical Genomics Analysis Branch, National Cancer Center, Goyang 10408, Republic of Korea, ²Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea and ³Department of Mathematics and Statistics, Boston University, Boston, MA 02215, USA

^†The authors wish it to be known that, in their opinion, the first three authors should be regarded as Joint First Authors.

^‡Principal investigators with equal contribution.

^*Correspondence may also be addressed Young Seok Ju

Somatic genome mutations occur due to combinations of various intrinsic/extrinsic mutational processes and DNA repair mechanisms. Different molecular processes frequently generate different signatures of somatic mutations in their own favored contexts. As a result, the regional somatic mutation rate is dependent on the local DNA sequence, the DNA replication/RNA transcription dynamics and epigenomic chromatin organization landscape in the genome. Here, we propose an online computational framework, termed Mutalisk, which correlates somatic mutations with various genomic, transcriptional and epigenomic features in order to understand mutational processes that contribute to the generation of the mutations. This user-friendly tool explores the presence of localized hypermutations (kataegis), dissects the spectrum of mutations into the maximum likelihood combination of known mutational signatures and associates the mutation density with numerous regulatory elements in the genome. As a result, global patterns of somatic mutations in any query sample can be efficiently screened, thus enabling a deeper understanding of various mutagenic factors. This tool will facilitate more effective downstream analyses of cancer genome sequences to elucidate the diversity of mutational processes underlying the development and clonal evolution of cancer cells. Mutalisk is freely available at http://mutalisk.org.