A substantial fraction of disease-causing mutations are pathogenic through aberrant splicing. Although genome profiling studies have identified somatic single-nucleotide variants (SNVs) in cancer, the extent to which these variants trigger abnormal splicing has not been systematically examined. Here we analyzed RNA sequencing and exome data from 1,812 patients with cancer and identified ∼900 somatic exonic SNVs that disrupt splicing. At least 163 SNVs, including 31 synonymous ones, were shown to cause intron retention or exon skipping in an allele-specific manner, with ∼70% of the SNVs occurring on the last base of exons. Notably, SNVs causing intron retention were enriched in tumor suppressors, and 97% of these SNVs generated a premature termination codon, leading to loss of function through nonsense-mediated decay or truncated protein. We also characterized the genomic features predictive of such splicing defects. Overall, this work demonstrates that intron retention is a common mechanism of tumor-suppressor inactivation.

Highlights d Driver fusion oncogenes in LADCs are generated from complex genomic rearrangements d These rearrangements are frequently copy-number balanced, resembling germline events d Fusions often arise in early decades of life, leaving long latency to diagnosis d SETD2 inactivation is cooperative with fusion oncogenes in TP53-wild-type LADCs

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.

Food waste accounts for a substantial portion of the organic waste generated at an increasing rate worldwide. Organic waste, including food waste, is largely subjected to landfill disposal, incineration, and anaerobic digestion; however, more sustainable methods are needed for treating it. Treatment of organic waste using black soldier fly (Hermetia illucens) larvae is an environmentally safe and cost-efficient method that has been attracting increasing attention worldwide. Black soldier fly decomposes various types of organic waste and converts them into high-value biomasses such as oils and proteins. This review introduces the trends in research related to the treatment of organic waste by black soldier fly (Hermetia illucens) larvae (BSFL) and their bioconversion efficiencies in Asian countries. Perspectives on the growth of BSFL during waste treatment operation and optimal rearing conditions are provided. The trends in studies related to the application of BSFL as biofuel and animal feed are also discussed. Such use of BSFL would be beneficial in Asia, especially in countries where the technology for processing organic waste is not readily available. This review may provide further directions of investigations including culture techniques for industrial scale applications of BSFL in food waste treatment and resource production in Asian countries.

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