Simultaneous profiling of transcriptome and DNA methylome from a single cell.

BackgroundSingle-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear.ResultsHere, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression.ConclusionsOur method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation

Reveal a hidden highly toxic substance in biochar to support its effective elimination strategy

With the aim to develop optimized biochar with minimal contaminants, it is important significance to broaden the understanding of biochar. Here, we disclose for the first time, a highly toxic substance (metal cyanide, MCN, such as KCN or NaCN) in biochar. The cyanide ion (CN−) content in biochar can be up to 85,870 mg/kg, which is determined by the inherent metal content and type in the biomass with K and Na increasing and Ca, Mg and Fe decreasing its formation. Density functional theory (DFT) analysis shows that unstable alkali oxygen-containing metal salts such as K2CO3 can induce an N rearrangement reaction to produce for example, KOCN. The strong reducing character of the carbon matrix further converts KOCN to KCN, thus resulting biochar with high risk. However, the stable Mg, Ca and Fe salts in biomass cannot induce an N rearrangement reaction due to their high binding energies. We therefore propose that high valent metal chloride salts such as FeCl3 and MgCl2 could be used to inhibit the production of cyanide via metal interactive reaction. These findings open a new point of view on the potential risk of biochar and provide a mitigation solution for biochar’s sustainable application

An Updated Search of Steady TeV γ−\gamma-Ray Point Sources in Northern Hemisphere Using the Tibet Air Shower Array

Using the data taken from Tibet II High Density (HD) Array (1997 February-1999 September) and Tibet-III array (1999 November-2005 November), our previous northern sky survey for TeV $\gamma-$ray point sources has now been updated by a factor of 2.8 improved statistics. From $0.0^{\circ}$ to $60.0^{\circ}$ in declination (Dec) range, no new TeV $\gamma-$ray point sources with sufficiently high significance were identified while the well-known Crab Nebula and Mrk421 remain to be the brightest TeV $\gamma-$ray sources within the field of view of the Tibet air shower array. Based on the currently available data and at the 90% confidence level (C.L.), the flux upper limits for different power law index assumption are re-derived, which are approximately improved by 1.7 times as compared with our previous reported limits.Comment: This paper has been accepted by hepn

Rational synthesis of an atomically precise carboncone under mild conditions

在已知的碳的存在形态中，还有一种锥型的碳结构，早在50年前人们在热解碳时发现了这类结构，此前也常被人们称为碳纳米锥，虽然这类碳纳米锥有望作为扫描隧道显微镜的探针、场发射头等替代材料，但始终未能找到合适方法精准地合成它们。因此，这类锥型碳材料尚未得到人们足够重视和开发。功能团簇材料创新研究群体的谢素原、张前炎课题组与美国波士顿学院的Lawrence Scott教授合作，首次通过有机合成途径，在温和的条件下合成得到了首例结构明确的碳锥单元（碳锥子）C70H20及其可溶衍生物。他们通过实验、理论计算、结构分析，最终在他们合成的碳锥子结构中，仅有1个五元环在锥顶，而在锥顶和锥缘之间（围绕着中心五元环）有2圈由六元环组成的完整的稠圈层，谢素原等将这一碳锥子命名为carboncone[1,2]。通过这一典型的碳锥子（carboncone[1,2]），有望借助气相沉积等技术不断增加稠圈层数（m）来制备具有确定锥角的系列单壁纳米碳锥（carboncone[1,m>2]）。随着研究的深入，不久的将来人类有望合成出其它四种不同锥角的碳锥子（carboncone[n=2-5,m]），完整地研究探索和开发利用这类锥型结构的碳材料。 化学化工学院2015级硕士生朱正钟（主要负责合成）和2017级博士生陈佐长（主要负责理论计算）为该论文的共同第一作者。Carboncones, a special family of all-carbon allotropes, are predicted to have unique properties that distinguish them from fullerenes, carbon nanotubes, and graphenes. Owing to the absence of methods to synthesize atomically well-defined carboncones, however, experimental insight into the nature of pure carboncones has been inaccessible. Herein, we describe a facile synthesis of an atomically well-defined carboncone[1,2] (C70H20) and its soluble penta-mesityl derivative. Identified by x-ray crystallography, the carbon skeleton is a carboncone with the largest possible apex angle. Much of the structural strain is overcome in the final step of converting the bowl-shaped precursor into the rigid carboncone under mild reaction conditions. This work provides a research opportunity for investigations of atomically precise single-layered carboncones having even higher cone walls and/or smaller apex angles.This research was supported by the National Natural Science Foundation of China (21771152, 21721001, 21390390, 21827801, 51572231, 21571151, and 21701134), the 973 Program of China (2015CB932301), the Major Science and Technology Project between University-Industry Cooperation in Fujian Province (2016H6023), and the Fundamental Research Funds for the Central Universities (20720170028 and 20720160084). This research was also supported financially by the U.S. National Science Foundation (CHE-0809494 and CHE-1149096). 研究工作得到国家自然科学基金（21771152等）、科技部重大科学研究计划项目（2015CB932301）和福建省高校产学合作项目、中央高校基本科研业务费、美国国家科学基金等的资助

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

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

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer