OGLE-2018-BLG-1011Lb,c: Microlensing planetary system with two giant planets orbiting a low-mass star

We report a multiplanetary system found from the analysis of microlensing event OGLE-2018-BLG-1011, for which the light curve exhibits a double-bump anomaly around the peak. We find that the anomaly cannot be fully explained by the binary-lens or binary-source interpretations and its description requires the introduction of an additional lens component. The 3L1S (three lens components and a single source) modeling yields three sets of solutions, in which one set of solutions indicates that the lens is a planetary system in a binary, while the other two sets imply that the lens is a multiplanetary system. By investigating the fits of the individual models to the detailed light curve structure, we find that the multiple-planet solution with planet-to-host mass ratios ∼9.5 ×10-3 and ∼15 ×10-3 are favored over the other solutions. From the Bayesian analysis, we find that the lens is composed of two planets with masses 1.8+3.4-1.1MJ and 2.8+5.11.7 MJ around a host with a mass 0.18 +0.33-0.10M0 and located at a distance 7.1+1.1-1.5 kpc. The estimated distance indicates that the lens is the farthest system among the known multiplanetary systems. The projected planet-host separations are a ⊥,2 = 1.8+2.1-1.5 au (0.8+0.9-0.6 au) and a ⊥,3 = 0.8+0.9-0.6 where the values of a ⊥,2 inside and outside the parenthesis are the separations corresponding to the two degenerate solutions, indicating that both planets are located beyond the snow line of the host, as with the other four multiplanetary systems previously found by microlensing

OGLE-2018-BLG-1011L\lowercase{b,c}: Microlensing Planetary System with Two Giant Planets Orbiting a Low-mass Star

We report a multiplanetary system found from the analysis of microlensing event OGLE-2018-BLG-1011, for which the light curve exhibits a double-bump anomaly around the peak. We find that the anomaly cannot be fully explained by the binary-lens or binary-source interpretations and its description requires the introduction of an additional lens component. The 3L1S (3 lens components and a single source) modeling yields three sets of solutions, in which one set of solutions indicates that the lens is a planetary system in a binary, while the other two sets imply that the lens is a multiplanetary system. By investigating the fits of the individual models to the detailed light curve structure, we find that the multiple-planet solution with planet-to-host mass ratios $\sim 9.5\times 10^{-3}$ and $\sim 15\times 10^{-3}$ are favored over the other solutions. From the Bayesian analysis, we find that the lens is composed of two planets with masses $1.8^{+3..4}_{-1.1}~M_{\rm J}$ and $2.8^{+5.1}_{-1.7}~M_{\rm J}$ around a host with a mass $0.18^{+0.33}_{-0.10}~M_\odot$ and located at a distance $7.1^{+1.1}_{-1.5}~{\rm kpc}$. The estimated distance indicates that the lens is the farthest system among the known multiplanetary systems. The projected planet-host separations are $a_{\perp,2}=1.8^{+2.1}_{-1.5}~{\rm au}$ ($0.8^{+0.9}_{-0.6}~{\rm au}$) and $a_{\perp,3}=0.8^{+0.9}_{-0.6}~{\rm au}$, where the values of $a_{\perp,2}$ in and out the parenthesis are the separations corresponding to the two degenerate solutions, indicating that both planets are located beyond the snow line of the host, as with the other four multiplanetary systems previously found by microlensing.Comment: 14 pages, 18 figures, 8 table

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

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

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.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 (VAFPeer reviewe

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

Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab.

Background: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models. Results: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5], and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata 35–<50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol but not vice versa. Conclusions: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01663402.gov; Unique identifier: NCT01663402.URL: https://www

Alirocumab and cardiovascular outcomes after acute coronary syndrome

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