A Bayesian Model for Detection of Highorder Interactions Among Genetic Variants in Genome-Wide Association Studies

Background: A central question for disease studies and crop improvements is how genetics variants drive phenotypes. Genome Wide Association Study (GWAS) provides a powerful tool for characterizing the genotypephenotype relationships in complex traits and diseases. Epistasis (gene-gene interaction), including high-order interaction among more than two genes, often plays important roles in complex traits and diseases, but current GWAS analysis usually just focuses on additive effects of single nucleotide polymorphisms (SNPs). The lack of effective computational modelling of high-order functional interactions often leads to significant under-utilization of GWAS data. Results: We have developed a novel Bayesian computational method with a Markov Chain Monte Carlo (MCMC) search, and implemented the method as a Bayesian High-order Interaction Toolkit (BHIT) for detecting epistatic interactions among SNPs. BHIT first builds a Bayesian model on both continuous data and discrete data, which is capable of detecting high-order interactions in SNPs related to case—control or quantitative phenotypes. We also developed a pipeline that enables users to apply BHIT on different species in different use cases. Conclusions: Using both simulation data and soybean nutritional seed composition studies on oil content and protein content, BHIT effectively detected some high-order interactions associated with phenotypes, and it outperformed a number of other available tools. BHIT is freely available for academic users at http://digbio.missouri.edu/BHIT/

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

X-ray spectrum emitted by the impact of Xe-129(26+) of the different kinetic energies on Au surface

<span style="color: rgb(51, 51, 51); font-family: arial, helvetica, sans-serif; font-size: 13px; line-height: 22px; background-color: rgb(248, 248, 248);">The characteristic X-ray spectra produced by the impact of Xe-129(26+) with kinetic energies from 350 to 600 keV and from 1.8 to 3.9 MeV on Au surface are measured. It is found that Xe-129(26+) with kinetic energies from 350 to 600 keV can excite only the characteristic X-ray spectra of M alpha of Au, but Xe-129(26+) with kinetic energies from 1.8 to 3.9 MeV can excite the characteristic X-ray spectra of M zeta, M alpha, M gamma and M delta. The relation between the characteristic X-ray intensity, the ratio of X-ray yield and the ion kinetic energy is analyzed. The kinetic energy threshold of L-X-ray of Xe emitted by Xe26+ is estimated.</span

X-ray spectrum emitted by the impact of Xe-129(q+) on Mo surface

We studied the characteristic X-ray spectra produced by the interaction of highly charged ions of X-129(q+) (q =25, 26, 27) with surface of metallic Mo. The experimental result shows that highly charged ions can excite the characteristic X-ray spectra of L-shell of Mo when the beam' s intensity is not more than 120 nA. The X-ray yield of single ion reaches a quantitative level of 10(-8) and increases with the increment of the ion' s kinetic energy and ionic charge (potential energy). By measuring the X-ray spectra of Mo-L alpha(1) the M-level lifetime of Mo atom is estimated by using Heisenberg uncertainty relation

Study of X-ray spectrum emitted due to the impact of Xe-129(q+) on different ion's charge on Au

<span style="color: rgb(51, 51, 51); font-family: arial, helvetica, sans-serif; font-size: 13px; line-height: 22px; background-color: rgb(248, 248, 248);">We report the experiment data of X-ray spectra produced by the impact of Xeq+ (q = 1 0, 15, 20, 26) with 2.4 MeV kinetic energy on Au surface in the National Laboratory of Heavy Ion Research Facility in Lanzhou. Results show that there is different broadening of Au M X-ray owing to multiply ionized effect in the collision with heavy ions, the degree of ionization mainly depends on the distribution of the electronic states in the ions&#39; outer shell. The yield of X-ray is calculated and compared with BEA (binary encounter approximation) model, and the effect of ion charge state on the X-ray yield is also discussed.</span