Gains in QTL Detection Using an Ultra-High Density SNP Map Based on Population Sequencing Relative to Traditional RFLP/SSR Markers

Huge efforts have been invested in the last two decades to dissect the genetic bases of complex traits including yields of many crop plants, through quantitative trait locus (QTL) analyses. However, almost all the studies were based on linkage maps constructed using low-throughput molecular markers, e.g. restriction fragment length polymorphisms (RFLPs) and simple sequence repeats (SSRs), thus are mostly of low density and not able to provide precise and complete information about the numbers and locations of the genes or QTLs controlling the traits. In this study, we constructed an ultra-high density genetic map based on high quality single nucleotide polymorphisms (SNPs) from low-coverage sequences of a recombinant inbred line (RIL) population of rice, generated using new sequencing technology. The quality of the map was assessed by validating the positions of several cloned genes including GS3 and GW5/qSW5, two major QTLs for grain length and grain width respectively, and OsC1, a qualitative trait locus for pigmentation. In all the cases the loci could be precisely resolved to the bins where the genes are located, indicating high quality and accuracy of the map. The SNP map was used to perform QTL analysis for yield and three yield-component traits, number of tillers per plant, number of grains per panicle and grain weight, using data from field trials conducted over years, in comparison to QTL mapping based on RFLPs/SSRs. The SNP map detected more QTLs especially for grain weight, with precise map locations, demonstrating advantages in detecting power and resolution relative to the RFLP/SSR map. Thus this study provided an example for ultra-high density map construction using sequencing technology. Moreover, the results obtained are helpful for understanding the genetic bases of the yield traits and for fine mapping and cloning of QTLs

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas.

DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in ∼20% of samples. Homologous recombination deficiency (HRD) was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein structure-based analyses allowed us to predict functional consequences of rare, recurrent DDR mutations. A new machine-learning-based classifier developed from gene expression data allowed us to identify alterations that phenocopy deleterious TP53 mutations. These frequent DDR gene alterations in many human cancers have functional consequences that may determine cancer progression and guide therapy

Observation of J/ψJ/\psi decays to e+e−e+e−e^{+}e^{-}e^{+}e^{-} and e+e−μ+μ−e^{+}e^{-}\mu^{+}\mu^{-}

Using a data sample of $4.481\times 10^8$ $\psi(3686)$ events collected with the BESIII detector, we report the first observation of the four-lepton-decays $J/\psi\to e^+e^-e^+e^-$ and $J/\psi\to e^+e^-\mu^+\mu^-$ utilizing the process $\psi(3686)\to \pi^+\pi^- J/\psi$. The branching fractions are determined to be $[4.32\pm0.26~(\rm stat)\pm0.19~(\rm syst)]\times 10^{-5}$ and $[2.45~\pm0.21~(\rm stat)\pm0.10~(\rm syst)]\times 10^{-5}$, respectively. The results deviate from theoretical predictions, by 2.8 and 5.2 $\sigma$, respectively. No significant signal is observed for $J/\psi\to \mu^+\mu^-\mu^+\mu^-$, and an upper limit on the branching fraction is set at $1.6\times 10^{-6}$ at the 90$\%$ confidence level. A CP asymmetry observable is constructed for the first two channels, which is measured to be $(-0.019\pm0.067\pm0.025)$ and $(-0.016\pm0.081\pm0.003)$, respectively. No evidence for CP violation is observed in this process.Comment: 9 pages, 1 figur

Observation of χcJ→ΛΛˉη\chi_{cJ}\to \Lambda\bar \Lambda \eta

By analyzing $(448.1\pm2.9)\times10^6$ $\psi(3686)$ events collected with the BESIII detector operating at the BEPCII collider, the decays of $\chi_{cJ} \to \Lambda\bar \Lambda \eta$ ($J=0$, 1 and 2) are observed for the first time with statistical significances of $13.9\sigma$, $6.7\sigma$, and $8.2\sigma$, respectively. The product branching fractions of $\psi(3686)\to\gamma\chi_{cJ}$ and $\chi_{cJ}\to \Lambda\bar \Lambda \eta$ are measured. Dividing by the world averages of the branching fractions of $\psi(3686)\to\gamma\chi_{cJ}$, the branching fractions of $\chi_{cJ}\to \Lambda\bar \Lambda \eta$ decays are determined to be $(2.31\pm0.30\pm0.21)\times10^{-4}$, $(5.86\pm1.38\pm0.68)\times10^{-5}$, and $(1.05\pm0.21\pm0.15)\times10^{-4}$ for $J=0$, 1 and 2, respectively, where the first uncertainties are statistical and the second systematic.Comment: 9 pages, 4 figure

Observation of the Y(4230)Y(4230) and evidence for a new vector charmonium-like state Y(4710)Y(4710) in e+e−→KS0KS0J/ψe^{+}e^{-}\to K_{S}^{0} K_{S}^{0} J/\psi

Cross sections for the process $e^{+} e^{-} \to K_{S}^{0} K_{S}^{0} J/\psi$ at center-of-mass energies from $4.128$ to $4.950$ GeV are measured using data samples with a total integrated luminosity of 21.2 fb$^{-1}$ collected by the BESIII detector operating at the BEPCII storage ring. The $Y(4230)$ state is observed in the energy dependence of the $e^{+} e^{-} \to K_{S}^{0} K_{S}^{0} J/\psi$ cross section for the first time with a statistical significance of 26.0$\sigma$. In addition, an enhancement around $4.710$ GeV, called the $Y(4710)$, is seen with a statistical significance of 4.2$\sigma$. There is no clear structure around $4.484$ GeV. Using a fit with a coherent sum of three Breit-Wigner functions, we determine the mass and width of the $Y(4230)$ state to be $4226.9 \pm 6.6 \pm 21.9$ MeV/$c^{2}$ and $71.7 \pm 16.2 \pm 31.4$ MeV, respectively, and the mass and width of the $Y(4710)$ state to be $4704.0 \pm 52.3 \pm 69.5$ MeV/$c^{2}$ and $183.2 \pm 114.0 \pm 90.8$ MeV, respectively, where the first uncertainties are statistical and the second are systematic. In addition, the average Born cross section ratio of $e^{+} e^{-} \to K_{S}^{0} K_{S}^{0} J/\psi$ to $e^{+} e^{-} \to K^{+} K^{-} J/\psi$ is measured to be $0.388_{-0.028}^{+0.035}\pm0.016$, or $0.426_{-0.031}^{+0.038}\pm0.018$ if three-body phase space is considered.Comment: Update draft based the comments from PRD refere