Structural variations (SVs) in cancer cells often impact large genomic regions with functional consequences. However, identification of SVs under positive selection is a challenging task because little is known about the genomic features related to the background breakpoint distribution in different cancers. We report a method that uses a generalized additive model to investigate the breakpoint proximity curves from 2,382 whole-genomes of 32 cancer types. We find that a multivariate model, which includes linear and nonlinear partial contributions of various tissue-specific features and their interaction terms, can explain up to 57% of the observed deviance of breakpoint proximity. In particular, three-dimensional genomic features such as topologically associating domains (TADs), TAD-boundaries and their interaction with other features show significant contributions. The model is validated by identification of known cancer genes and revealed putative drivers in cancers different than those with previous evidence of positive selection.
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http://dx.doi.org/10.1038/s41467-022-32945-2 | DOI Listing |
Nat Chem Biol
October 2024
Department of Chemistry, Princeton University, Princeton, NJ, USA.
The post-translational regulation of protein function is involved in most cellular processes. As such, synthetic biology tools that operate at this level provide opportunities for manipulating cellular states. Here we deploy proximity-triggered protein trans-splicing technology to enable the time-resolved synthesis of target proteins from premade parts.
View Article and Find Full Text PDFWhen the critical dimension (CD) of resist patterns nears the resolution limit of the digital micromirror device (DMD) maskless projection lithography (DMD-MPL), significant distortion can emerge in the silicon wafer due to the optical proximity effect (OPE). The significant distortion (breakpoints, line-end scaling, corner rounding, etc.) between resist patterns and target patterns results in reduced lithographic quality.
View Article and Find Full Text PDFHGG Adv
April 2024
School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy. Electronic address:
BMC Med Genomics
November 2023
Prenatal Diagnosis Center, Zhongshan Boai Hospital Affiliated to Southern Medical University, Zhongshan, Guangdong, China.
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