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Open AccessArticle

Nucleotide Weight Matrices Reveal Ubiquitous Mutational Footprints of AID/APOBEC Deaminases in Human Cancer Genomes

1
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894-6075, USA
2
Center for Collaborative Research in Health Disparities–RCMI Program, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA
3
Department Microbiology and Molecular Genetics, University of California, Davis, CA 95616, USA
4
Institute of Cytology and Genetics, Novosibirsk 630090, Russia
5
Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
6
Institute of Medical Genetics, Cardiff University, Cardiff CF14 4AY, UK
7
Departments of Microbiology and Pathology; Biochemistry and Molecular Biology; Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA
8
Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE 68198, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Cancers 2019, 11(2), 211; https://doi.org/10.3390/cancers11020211
Received: 11 January 2019 / Revised: 30 January 2019 / Accepted: 30 January 2019 / Published: 12 February 2019
(This article belongs to the Special Issue Application of Bioinformatics in Cancers)
Cancer genomes accumulate nucleotide sequence variations that number in the tens of thousands per genome. A prominent fraction of these mutations is thought to arise as a consequence of the off-target activity of DNA/RNA editing cytosine deaminases. These enzymes, collectively called activation induced deaminase (AID)/APOBECs, deaminate cytosines located within defined DNA sequence contexts. The resulting changes of the original C:G pair in these contexts (mutational signatures) provide indirect evidence for the participation of specific cytosine deaminases in a given cancer type. The conventional method used for the analysis of mutable motifs is the consensus approach. Here, for the first time, we have adopted the frequently used weight matrix (sequence profile) approach for the analysis of mutagenesis and provide evidence for this method being a more precise descriptor of mutations than the sequence consensus approach. We confirm that while mutational footprints of APOBEC1, APOBEC3A, APOBEC3B, and APOBEC3G are prominent in many cancers, mutable motifs characteristic of the action of the humoral immune response somatic hypermutation enzyme, AID, are the most widespread feature of somatic mutation spectra attributable to deaminases in cancer genomes. Overall, the weight matrix approach reveals that somatic mutations are significantly associated with at least one AID/APOBEC mutable motif in all studied cancers. View Full-Text
Keywords: DNA sequence profile; Monte Carlo; mixture of normal distributions; somatic mutation; tumor; mutable motif; activation induced deaminase; AID/APOBEC DNA sequence profile; Monte Carlo; mixture of normal distributions; somatic mutation; tumor; mutable motif; activation induced deaminase; AID/APOBEC
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MDPI and ACS Style

Rogozin, I.B.; Roche-Lima, A.; Lada, A.G.; Belinky, F.; Sidorenko, I.A.; Glazko, G.V.; Babenko, V.N.; Cooper, D.N.; Pavlov, Y.I. Nucleotide Weight Matrices Reveal Ubiquitous Mutational Footprints of AID/APOBEC Deaminases in Human Cancer Genomes. Cancers 2019, 11, 211. https://doi.org/10.3390/cancers11020211

AMA Style

Rogozin IB, Roche-Lima A, Lada AG, Belinky F, Sidorenko IA, Glazko GV, Babenko VN, Cooper DN, Pavlov YI. Nucleotide Weight Matrices Reveal Ubiquitous Mutational Footprints of AID/APOBEC Deaminases in Human Cancer Genomes. Cancers. 2019; 11(2):211. https://doi.org/10.3390/cancers11020211

Chicago/Turabian Style

Rogozin, Igor B.; Roche-Lima, Abiel; Lada, Artem G.; Belinky, Frida; Sidorenko, Ivan A.; Glazko, Galina V.; Babenko, Vladimir N.; Cooper, David N.; Pavlov, Youri I. 2019. "Nucleotide Weight Matrices Reveal Ubiquitous Mutational Footprints of AID/APOBEC Deaminases in Human Cancer Genomes" Cancers 11, no. 2: 211. https://doi.org/10.3390/cancers11020211

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