Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Kajian literatur efektivitas dan keamanan empagliflozin pada pasien diabetes mellitus tipe 2 dengan komplikasi gagal jantung kongestif

Diabetes mellitus merupakan suatu kelompok penyakit metabolik dengan karakteristik hiperglikemia yang terjadi karena kelainan sekresi insulin, kerja insulin, atau kedua-duanya. Diabetes Mellitus diklasifikasikan menjadi 4 kategori yaitu Diabetes mellitus tipe 1, DM tipe 2, DM gestasional, dan DM tipe lain. DM tipe 2 menyumbang antara 90% sampai 95% dari diabetes. Empagliflozin merupakan obat golongan SGLT-2 inhibitor yang direkomendasikan oleh ADA pada pasien DMT2 dengan penyakit kardiovaskular aterosklerotik (ASCVD), gagal ginjal kronis, dan gagal jantung. Empagliflozin bekerja dengan cara menghambat reabsorbsi glukosa di tubulus proksimal dan memfasilitasi ekskresi glukosa melalui urin, sehingga dapat memperbaiki kontrol glikemik. Kajian literatur ini bertujuan untuk mengetahui efektivitas dan keamanan penggunaan terapi empagliflozin pada pasien DMT2 dengan komplikasi gagal jantung atau penyakit kardiovaskular lainnya. Proses pencarian artikel dalam kajian literatur ini menggunakan database PubMed dengan kombinasi kata kunci ("Diabetes Mellitus, Type 2/complications"[Mesh]) AND "empagliflozin" [Supplementary Concept], dan didapatkan 10 artikel yang memenuhi kriteria inklusi, yaitu 8 artikel dengan metode Randomized Con trol Trial (RCT) dan 2 artikel dengan metode Cohort. Hasil kajian literatur dari 10 artikel, menunjukkan bahwa Empagliflozin memiliki efektivitas dalam memperbaiki kondisi kardiovaskular pada pasien DMT2 dengan menurunkan HbA1c, tekanan darah, kejadian rawat inap gagal jantung, kematian akibat kardiovaskular, menurunkan angka kejadian major adverse Cardiovascular Event (MACE), dan mempunyai efek renoprotektif. Efek samping terjadi pada penggunaan empagliflozin adalah infeksi genital, infeksi saluran kemih, deplesi volume, dan ketoasidosis

MOESM3 of Modeling human enteric dysbiosis and rotavirus immunity in gnotobiotic pigs

Additional file 3: Figure S2. Jejunum Histopathology. Representative photomicrographs of jejunum sections from a pig in each group at each time point. A. HHGM PID 28, B. HHGM PCD 7, C. UHGM PID28, D. UHGM PCD7. There are no significant histologic differences between the groups. Scale bar is 200 Îźm

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts