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Pan Genome

Assaf C Bester, Jonathan D Lee, Alejandro Chavez, Yu-Ru Lee, Daphna Nachmani, Suhani Vora, Joshua Victor, Martin Sauvageau, Emanuele Monteleone, John L Rinn, Paolo Provero, George M Church, John G Clohessy, Pier Paolo Pandolfi
Resistance to chemotherapy plays a significant role in cancer mortality. To identify genetic units affecting sensitivity to cytarabine, the mainstay of treatment for acute myeloid leukemia (AML), we developed a comprehensive and integrated genome-wide platform based on a dual protein-coding and non-coding integrated CRISPRa screening (DICaS). Putative resistance genes were initially identified using pharmacogenetic data from 760 human pan-cancer cell lines. Subsequently, genome scale functional characterization of both coding and long non-coding RNA (lncRNA) genes by CRISPR activation was performed...
April 19, 2018: Cell
Yangqing Deng, Wei Pan
Due to issues of practicality and confidentiality of genomic data-sharing on a large scale, typically only meta- or mega-analyzed GWAS summary data, not individual-level data, are publicly available. Re-analyses of such GWAS summary data for a wide range of applications have become more and more common and useful, which often require the use of an external reference panel with individual-level genotypic data to infer linkage disequilibrium (LD) among genetic variants. However, with a small sample size in only hundreds, as for the most popular 1000 Genomes Project European sample, estimation errors for LD are not negligible, leading to often dramatically increased numbers of false positives in subsequent analyses of GWAS summary data...
April 19, 2018: Genetics
Jiale Ma, Min Sun, Zihao Pan, Chengping Lu, Huochun Yao
The type VI secretion system (T6SS) is considered as one of the key competition strategies by injecting toxic effectors for intestinal pathogens to acquire optimal colonization in host gut, a microenviroment with high-density polymicrobial community where bacteria compete for niches and resources. Enterotoxigenic Escherichia coli (ETEC), a major cause of infectious diarrhea in human and animals, widely encode T6SS clusters in their genomes. In this report, we first identified VT1, a novel amidase effector in ETEC, significantly hydrolyzed D-lactyl-L-Ala crosslinks between N-acetylmuramoyl and L-Ala in peptidoglycan...
April 16, 2018: Biochimica et Biophysica Acta
Jonathan Z Pan
Although general anesthesia induced by inhaled anesthetics produces definitive phenotypes (e.g., loss of mobility, amnesia, analgesia), the underlying targets of these drugs are still not clear. Genomics and proteomic techniques are discussed for measurement of global transcriptional and translational changes after inhaled anesthetic exposures. The current discussion focuses primarily on the genomic and proteomic technical methodology. We also include a discussion of network and pathway analyses for data interpretation after identification of the targets...
2018: Methods in Enzymology
Nannan Liu, Jianxiao Liu, Wenqiang Li, Qingchun Pan, Jie Liu, Xiaohong Yang, Jianbing Yan, Yingjie Xiao
BACKGROUND: Residual heterozygosity (RH) in advanced inbred lines of plants benefits quantitative trait locus (QTL) mapping studies. However, knowledge of factors affecting the genome-wide distribution of RH remains limited. RESULTS: A set of 2196 heterogeneous inbred family (HIF) maize lines derived from 12 recombinant inbred line (RIL) populations was genotyped using the Maize50K SNP chip. A total of 18,615 unique RH intervals were identified, ranging from 505 to 2095 intervals per population, with average maize genome coverage of 94...
April 19, 2018: BMC Plant Biology
Ming Wang, QingXiang Gao, Xu Teng, MeiPing Pan, TianMiao Lin, GuiXuan Zhou, BenHua Xu, ZhiCao Yue
Ultraviolet radiation (UVR) and ionizing radiation (IR) are common genotoxic stresses that damage human skin, although the specific damages to the genomic DNA are different. Here we show that in the mouse glabrous skin, both UVR and IR induce DNA damage, cell cycle arrest, and condensed cell nuclei. However, only IR induces mitotic catastrophe (MC) in the epidermis. This is because UVR induces a complete blockage of pRB phosphorylation and cell cycle arrest in the G1 phase, whereas pRB phosphorylation remains positive in a significant portion of the epidermal keratinocytes following IR exposure...
April 19, 2018: Experimental Dermatology
Q Wang, J Pi, J Shen, A Pan, L Qu
Rumplessness in Hongshan chickens has been reported as a novel sex-linked characteristic. Re-sequencing data suggest that a pseudogene on the Z chromosome, LOC431648, is affiliated with this phenotype. In this study, we chose 23 rumpless and 25 normal Hongshan chickens to localize the potential variation by means of a genome-wide association study using a high density microarray. A region on the Z chromosome was found to be closely associated with rumplessness in Hongshan chickens. The region, located in gene LINGO2, was approximately 3 Mb away from pseudogene LOC431648...
April 19, 2018: Animal Genetics
Anchal Sharma, Chuan Jiang, Subhajyoti De
Although the catalog of cancer-associated mutations in protein-coding regions is nearly complete for all major cancer types, an assessment of regulatory changes in cancer genomes and their clinical significance remain largely preliminary. Adopting bottom-up approach, we quantify the effects of different sources of gene expression variation in a cohort of 3899 samples from 10 cancer types. We find that copy number alterations, epigenetic changes, transcription factors and microRNAs collectively explain, on average, only 31-38% and 18-26% expression variation for cancer-associated and other genes, respectively, and that among these factors copy number alteration has the highest effect...
April 17, 2018: Nucleic Acids Research
Hung-Yin Pan, Carton W Chen, Chih-Hung Huang
Soil bacteria Streptomyces are the most important producers of secondary metabolites, including most known antibiotics. These bacteria and their close relatives are unique in possessing linear chromosomes, which typically harbor 20 to 30 biosynthetic gene clusters of tens to hundreds of kb in length. Many Streptomyces chromosomes are accompanied by linear plasmids with sizes ranging from several to several hundred kb. The large linear plasmids also often contain biosynthetic gene clusters. We have developed a targeted recombination procedure for arm exchanges between a linear plasmid and a linear chromosome...
April 17, 2018: Journal of General and Applied Microbiology
Luis Pedro Coelho, Jens Roat Kultima, Paul Igor Costea, Coralie Fournier, Yuanlong Pan, Gail Czarnecki-Maulden, Matthew Robert Hayward, Sofia K Forslund, Thomas Sebastian Benedikt Schmidt, Patrick Descombes, Janet R Jackson, Qinghong Li, Peer Bork
BACKGROUND: Gut microbes influence their hosts in many ways, in particular by modulating the impact of diet. These effects have been studied most extensively in humans and mice. In this work, we used whole genome metagenomics to investigate the relationship between the gut metagenomes of dogs, humans, mice, and pigs. RESULTS: We present a dog gut microbiome gene catalog containing 1,247,405 genes (based on 129 metagenomes and a total of 1.9 terabasepairs of sequencing data)...
April 19, 2018: Microbiome
Zhangyuan Pan, Shengdi Li, Qiuyue Liu, Zhen Wang, Zhengkui Zhou, Ran Di, Benpeng Miao, Wenping Hu, Xiangyu Wang, Xiaoxiang Hu, Ze Xu, Dongkai Wei, Xiaoyun He, Liyun Yuan, Xiaofei Guo, Benmeng Liang, Ruichao Wang, Xiaoyu Li, Xiaohan Cao, Xinlong Dong, Qing Xia, Hongcai Shi, Geng Hao, Jean Yang, Cuicheng Luosang, Yiqiang Zhao, Mei Jin, Yingjie Zhang, Shenjin Lv, Fukuan Li, Guohui Ding, Mingxing Chu, Yixue Li
Background: Animal domestication has been extensively studied, but the process of feralization remains poorly understood. Results: Here, we performed whole-genome sequencing of 99 sheep and identified a primary genetic divergence between 2 heterogeneous populations in the Tibetan Plateau, including 1 semi-feral lineage. Selective sweep and candidate gene analysis revealed local adaptations of these sheep associated with sensory perception, muscle strength, eating habit, mating process, and aggressive behavior...
April 1, 2018: GigaScience
David Z Pan, Kristina M Garske, Marcus Alvarez, Yash V Bhagat, James Boocock, Elina Nikkola, Zong Miao, Chelsea K Raulerson, Rita M Cantor, Mete Civelek, Craig A Glastonbury, Kerrin S Small, Michael Boehnke, Aldons J Lusis, Janet S Sinsheimer, Karen L Mohlke, Markku Laakso, Päivi Pajukanta, Arthur Ko
Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic and molecular mechanisms that underlie obesity-related phenotypes can help to improve treatment options and drug development. Here we perform promoter Capture Hi-C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression...
April 17, 2018: Nature Communications
Andrew M Hudson, Natalie L Stephenson, Cynthia Li, Eleanor Trotter, Adam J Fletcher, Gitta Katona, Patrycja Bieniasz-Krzywiec, Matthew Howell, Chris Wirth, Simon Furney, Crispin J Miller, John Brognard
A major challenge in cancer genomics is identifying "driver" mutations from the many neutral "passenger" mutations within a given tumor. To identify driver mutations that would otherwise be lost within mutational noise, we filtered genomic data by motifs that are critical for kinase activity. In the first step of our screen, we used data from the Cancer Cell Line Encyclopedia and The Cancer Genome Atlas to identify kinases with truncation mutations occurring within or before the kinase domain...
April 17, 2018: Science Signaling
David Tamborero, Carlota Rubio-Perez, Ferran Muiños, Radhakrishnan Sabarinathan, Josep Maria Piulats, Aura Muntasell, Rodrigo Dienstmann, Nuria Lopez-Bigas, Abel Gonzalez-Perez
PURPOSE: Throughout their development tumors are challenged by the immune system and they acquire features to evade its surveillance. A systematic view of these traits which sheds light on how tumors respond to immunotherapies is still lacking. EXPERIMENTAL DESIGN: Here, we computed the relative abundance of an array of immune cell populations to measure the immune infiltration pattern of 9,174 tumors of 29 solid cancers. We then clustered tumors with similar infiltration pattern to define immune-phenotypes...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Xianli Shi, Mingwei Wang, A Y Abdullahi, Yeqi Fu, Fang Yang, Xingang Yu, Weida Pan, Xinxin Yan, Jianxiong Hang, Pan Zhang, Guoqing Li
Ancylostoma ceylanicum may inhabit the small intestine of canids, felids and humans, can pose a potential risk to public health. This study is the first time to amplify complete mitochondrial genome sequence of A. ceylanicum from dog and to compare it with Ancylostoma tubaeforme, Ancylostoma duodenale and Ancylostoma caninum. The results showed that the complete mitochondrial genome of A. ceylanicum was 13,660 bp in length, including 12 protein-coding genes, 2 rRNA genes and 22 tRNA genes and 3 non-coding regions (AT-rich region, SNCR and LNCR)...
April 13, 2018: Infection, Genetics and Evolution
Jiajia Yang, Yao Lin, Liming Jiang, Juemin Xi, Xiaodan Wang, Jiaoqiong Guan, Junying Chen, Yue Pan, Jia Luo, Chao Ye, Qiangming Sun
To elucidate the differences in microRNAs during dengue virus infection between Vero cell-adapted strain (DENV-2-Vero) and its source, the clinical C6/36 isolated strain (DENV-2-C6/36), a comparison analysis was performed in Vero cells by high throughput sequencing. The results showed that the expression of 16 known and 3 novel miRNAs exhibited marked differences. 5 known miRNAs were up-regulated in DENV-2-C6/36 group, while 11 known microRNAs were down-regulated in DENV-2-Vero group. The GO enrichment and KEGG pathway analysis showed that there was a distinct difference in regulating viral replication between two strains...
April 13, 2018: Virus Research
Antoine Simoneau, Étienne Ricard, Hugo Wurtele
The evolutionarily-conserved sirtuin family of histone deacetylases regulates a multitude of DNA-associated processes. A recent genome-wide screen conducted in the yeast Saccharomyces cerevisiae identified Yku70/80, which regulate nonhomologous end-joining (NHEJ) and telomere structure, as being essential for cell proliferation in the presence of the pan-sirtuin inhibitor nicotinamide (NAM). Here, we show that sirtuin-dependent deacetylation of both histone H3 lysine 56 and H4 lysine 16 promotes growth of yku70Δ and yku80Δ cells, and that the NAM sensitivity of these mutants is not caused by defects in double-strand break repair by NHEJ, but rather by their inability to maintain normal telomere length...
April 16, 2018: PLoS Genetics
Rob J A Verhoeven, Shuang Tong, Jingfeng Zong, Yixin Chen, Sai-Wah Tsao, Jianji Pan, Honglin Chen
Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is one of the few viral proteins expressed by EBV in nasopharyngeal carcinoma (NPC), most likely because of its essential role in maintaining the viral genome in EBV-infected cells. In NPC, EBNA1 expression is driven by the Bam HI-Q promoter (Qp), which is regulated by both cellular and viral factors. We previously determined that the expression of another group of EBV transcripts, Bam HI-A rightward transcripts (BARTs), is associated with constitutively activated nuclear factor-κB (NF-κB) signaling in NPC cells...
April 16, 2018: Cancers
Zhuoxuan Wu, Zhen Liu, Weiting Ge, Jiawei Shou, Liangkun You, Hongming Pan, Weidong Han
This study aimed to identify differentially expressed genes (DEGs) related to the colorectal normal mucosa-adenoma-carcinoma sequence using bioinformatics analysis. Raw data files were downloaded from Gene Expression Omnibus (GEO) and underwent quality assessment and preprocessing. DEGs were analyzed by the limma package in R software (R version 3.3.2). Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed with the DAVID online tool. In a comparison of colorectal adenoma (n = 20) and colorectal cancer (CRC) stage I (n = 31), II (n = 38), III (n = 45), and IV (n = 62) with normal colorectal mucosa (n = 19), we identified 336 common DEGs...
April 16, 2018: Cancer Medicine
Jun Gong, Kathy Pan, Marwan Fakih, Sumanta Pal, Ravi Salgia
Advancements in next-generation sequencing have greatly enhanced the development of biomarker-driven cancer therapies. The affordability and availability of next-generation sequencers have allowed for the commercialization of next-generation sequencing platforms that have found widespread use for clinical-decision making and research purposes. Despite the greater availability of tumor molecular profiling by next-generation sequencing at our doorsteps, the achievement of value-based care, or improving patient outcomes while reducing overall costs or risks, in the era of precision oncology remains a looming challenge...
March 20, 2018: Oncotarget
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