المؤلفون: Jiang, Runze, Lu, Yi-Tsung, Ho, Hao, Li, Bo, Chen, Jie-Fu, Lin, Millicent, Li, Fuqiang, Wu, Kui, Wu, Hanjie, Lichterman, Jake, Wan, Haolei, Lu, Chia-Lun, OuYang, William, Ni, Ming, Wang, Linlin, Li, Guibo, Lee, Tom, Zhang, Xiuqing, Yang, Jonathan, Rettig, Matthew, Chung, Leland WK, Yang, Huanming, Li, Ker-Chau, Hou, Yong, Tseng, Hsian-Rong, Hou, Shuang, Xu, Xun, Wang, Jun, Posadas, Edwin M

المصدر: Oncotarget. 6(42)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Genetics, Biotechnology, Urologic Diseases, Clinical Research, Human Genome, Prostate Cancer, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Base Sequence, Biomarkers, Tumor, Biopsy, Cell Separation, Chromosomes, Human, DNA Mutational Analysis, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Rearrangement, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Laser Capture Microdissection, Liver Neoplasms, Male, Molecular Sequence Data, Mutation, Nanotechnology, Neoplastic Cells, Circulating, Oligonucleotide Array Sequence Analysis, Phenotype, Polymorphism, Single Nucleotide, Predictive Value of Tests, Prostatic Neoplasms, Time Factors, circulating tumor cell, prostate cancer, whole genome sequencing, liquid biopsy, cancer heterogeneity, Oncology and carcinogenesis

الوصف: Previous studies have demonstrated focal but limited molecular similarities between circulating tumor cells (CTCs) and biopsies using isolated genetic assays. We hypothesized that molecular similarity between CTCs and tissue exists at the single cell level when characterized by whole genome sequencing (WGS). By combining the NanoVelcro CTC Chip with laser capture microdissection (LCM), we developed a platform for single-CTC WGS. We performed this procedure on CTCs and tissue samples from a patient with advanced prostate cancer who had serial biopsies over the course of his clinical history. We achieved 30X depth and ≥ 95% coverage. Twenty-nine percent of the somatic single nucleotide variations (SSNVs) identified were founder mutations that were also identified in CTCs. In addition, 86% of the clonal mutations identified in CTCs could be traced back to either the primary or metastatic tumors. In this patient, we identified structural variations (SVs) including an intrachromosomal rearrangement in chr3 and an interchromosomal rearrangement between chr13 and chr15. These rearrangements were shared between tumor tissues and CTCs. At the same time, highly heterogeneous short structural variants were discovered in PTEN, RB1, and BRCA2 in all tumor and CTC samples. Using high-quality WGS on single-CTCs, we identified the shared genomic alterations between CTCs and tumor tissues. This approach yielded insight into the heterogeneity of the mutational landscape of SSNVs and SVs. It may be possible to use this approach to study heterogeneity and characterize the biological evolution of a cancer during the course of its natural history.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9vx810dqTest

المؤلفون: Li, Ker-Chau, Palotie, Aarno, Yuan, Shinsheng, Bronnikov, Denis, Chen, Daniel, Wei, Xuelian, Choi, Oi-Wa, Saarela, Janna, Peltonen, Leena

المصدر: Genome Biology. 8(10)

مصطلحات موضوعية: Biological Sciences, Bioinformatics and Computational Biology, Computational Biology, Excitatory Amino Acid Transporter 1, Finland, Gene Expression, Genetic Predisposition to Disease, Genetic Testing, Genomics, Genotype, Humans, Multiple Sclerosis, Protein Kinase C-alpha, Environmental Sciences, Information and Computing Sciences, Bioinformatics

الوصف: A novel approach to finding candidate genes by using gene expression data through liquid association is developed and used to identify multiple sclerosis susceptibility candidate genes.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2hx105b3Test

المؤلفون: Sun, Wei, Xie, Wei, Xu, Feng, Grunstein, Michael, Li, Ker-Chau

المصدر: PloS One, 4(3)

مصطلحات موضوعية: Nucleosomes, Histones, Markov Chains, Animals, Chromosome Mapping, Humans, DNA, Intergenic, Genomics

الوصف: BackgroundNucleosome free regions (NFRs) play important roles in diverse biological processes including gene regulation. A genome-wide quantitative portrait of each individual NFR, with their starting and ending positions, lengths, and degrees of nucleosome depletion is critical for revealing the heterogeneity of gene regulation and chromatin organization. By averaging nucleosome occupancy levels, previous studies have identified the presence of NFRs in the promoter regions across many genes. However, evaluation of the quantitative characteristics of individual NFRs requires an NFR calling method.MethodologyIn this study, we propose a statistical method to identify the patterns of NFRs from a genome-wide measurement of nucleosome occupancy. This method is based on an appropriately designed segmental semi-Markov model, which can capture each NFR pattern and output its quantitative characterizations. Our results show that the majority of the NFRs are located in intergenic regions or promoters with a length of about 400–600bp and varying degrees of nucleosome depletion. Our quantitative NFR mapping allows for an investigation of the relative impacts of transcription machinery and DNA sequence in evicting histones from NFRs. We show that while both factors have significant overall effects, their specific contributions vary across different subtypes of NFRs.ConclusionThe emphasis of our approach on the variation rather than the consensus of nucleosome free regions sets the tone for enabling the exploration of many subtler dynamic aspects of chromatin biology.

العلاقة: https://doi.org/10.17615/h44t-db89Test; https://cdr.lib.unc.edu/downloads/n009w926c?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/n009w926cTest

الإتاحة: https://doi.org/10.17615/h44t-db89Test
https://cdr.lib.unc.edu/downloads/n009w926c?file=thumbnailTest
https://cdr.lib.unc.edu/downloads/n009w926cTest

المؤلفون: Liu, Chia-Hsin, Ho, Bing-Ching, Chen, Chun-Ling, Chang, Ya-Hsuan, Hsu, Yi-Chiung, Li, Yu-Cheng, Yuan, Shin-Sheng, Huang, Yi-Huan, Chang, Chi-Sheng, Li, Ker-Chau, Chen, Hsuan-Yu

المصدر: PLoS ONE; 2/9/2016, Vol. 11 Issue 2, p1-14, 14p

مصطلحات موضوعية: NUCLEOTIDE sequencing, CHROMATIN, IMMUNOPRECIPITATION, BINDING sites, HISTONES

مستخلص: Recently, with the development of next generation sequencing (NGS), the combination of chromatin immunoprecipitation (ChIP) and NGS, namely ChIP-seq, has become a powerful technique to capture potential genomic binding sites of regulatory factors, histone modifications and chromatin accessible regions. For most researchers, additional information including genomic variations on the TF binding site, allele frequency of variation between different populations, variation associated disease, and other neighbour TF binding sites are essential to generate a proper hypothesis or a meaningful conclusion. Many ChIP-seq datasets had been deposited on the public domain to help researchers make new discoveries. However, researches are often intimidated by the complexity of data structure and largeness of data volume. Such information would be more useful if they could be combined or downloaded with ChIP-seq data. To meet such demands, we built a webtool: ePIgenomic ANNOtation tool (ePIANNO, ). ePIANNO is a web server that combines SNP information of populations (1000 Genomes Project) and gene-disease association information of GWAS (NHGRI) with ChIP-seq (hmChIP, ENCODE, and ROADMAP epigenomics) data. ePIANNO has a user-friendly website interface allowing researchers to explore, navigate, and extract data quickly. We use two examples to demonstrate how users could use functions of ePIANNO webserver to explore useful information about TF related genomic variants. Users could use our query functions to search target regions, transcription factors, or annotations. ePIANNO may help users to generate hypothesis or explore potential biological functions for their studies. [ABSTRACT FROM AUTHOR]

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