Karolak, Aleksandra; Levatic, Jurica; Supek, Fran published the artcile< A framework for mutational signature analysis based on DNA shape parameters>, Synthetic Route of 112-63-0, the main research area is DNA sequence mutational signature oligonucleotides mutagenesis.
The mutation risk of a DNA locus depends on its oligonucleotide context. In turn, mutability of oligonucleotides varies across individuals, due to exposure to mutagenic agents or due to variable efficiency and/or accuracy of DNA repair. Such variability is captured by mutational signatures, a math. construct obtained by a deconvolution of mutation frequency spectra across individuals. There is a need to enhance methods for inferring mutational signatures to make better use of sparse mutation data (e.g., resulting from exome sequencing of cancers), to facilitate insight into underlying biol. mechanisms, and to provide more accurate mutation rate baselines for inferring pos. and neg. selection. We propose a conceptualization of mutational signatures that represents oligonucleotides via descriptors of DNA conformation: base pair, base pair step, and minor groove width parameters. We demonstrate how such DNA structural parameters can accurately predict mutation occurrence due to DNA repair failures or due to exposure to diverse mutagens such as radiation, chem. exposure, and the APOBEC cytosine deaminase enzymes. Furthermore, the mutation frequency of DNA oligomers classed by structural features can accurately capture systematic variability in mutagenesis of >1,000 tumors originating from diverse human tissues. A nonneg. matrix factorization was applied to mutation spectra stratified by DNA structural features, thereby extracting novel mutational signatures. Moreover, many of the known trinucleotide signatures were associated with an addnl. spectrum in the DNA structural descriptor space, which may aid interpretation and provide mechanistic insight. Overall, we suggest that the power of DNA sequence motif-based mutational signature anal. can be enhanced by drawing on DNA shape features.
PLoS One published new progress about B-cell lymphoma. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Synthetic Route of 112-63-0.
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