%0 Journal Article %J BMC Bioinformatics %D 2016 %T DNAism: exploring genomic datasets on the web with Horizon Charts. %A Rio Deiros, David %A Gibbs, Richard A %A Rogers, Jeffrey %K Computational Biology %K Computer Graphics %K Datasets as Topic %K Gene Library %K Genome, Human %K Genomics %K Humans %K Internet %K Software %X

BACKGROUND: Computational biologists daily face the need to explore massive amounts of genomic data. New visualization techniques can help researchers navigate and understand these big data. Horizon Charts are a relatively new visualization method that, under the right circumstances, maximizes data density without losing graphical perception.

RESULTS: Horizon Charts have been successfully applied to understand multi-metric time series data. We have adapted an existing JavaScript library (Cubism) that implements Horizon Charts for the time series domain so that it works effectively with genomic datasets. We call this new library DNAism.

CONCLUSIONS: Horizon Charts can be an effective visual tool to explore complex and large genomic datasets. Researchers can use our library to leverage these techniques to extract additional insights from their own datasets.

%B BMC Bioinformatics %V 17 %P 49 %8 2016 Jan 27 %G eng %1 https://www.ncbi.nlm.nih.gov/pubmed/26819101?dopt=Abstract %R 10.1186/s12859-016-0891-2 %0 Journal Article %J Genome Res %D 2016 %T The population genomics of rhesus macaques (Macaca mulatta) based on whole-genome sequences. %A Xue, Cheng %A Raveendran, Muthuswamy %A Harris, R Alan %A Fawcett, Gloria L %A Liu, Xiaoming %A White, Simon %A Dahdouli, Mahmoud %A Rio Deiros, David %A Below, Jennifer E %A Salerno, William %A Cox, Laura %A Fan, Guoping %A Ferguson, Betsy %A Horvath, Julie %A Johnson, Zach %A Kanthaswamy, Sree %A Kubisch, H Michael %A Liu, Dahai %A Platt, Michael %A Smith, David G %A Sun, Binghua %A Vallender, Eric J %A Wang, Feng %A Wiseman, Roger W %A Chen, Rui %A Muzny, Donna M %A Gibbs, Richard A %A Yu, Fuli %A Rogers, Jeffrey %K Animals %K Evolution, Molecular %K Female %K Genetic Fitness %K High-Throughput Nucleotide Sequencing %K Macaca mulatta %K Models, Animal %K Polymorphism, Single Nucleotide %K Population Density %K Whole Genome Sequencing %X

Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate in biomedical research, have the largest natural geographic distribution of any nonhuman primate, and have been the focus of much evolutionary and behavioral investigation. Consequently, rhesus macaques are one of the most thoroughly studied nonhuman primate species. However, little is known about genome-wide genetic variation in this species. A detailed understanding of extant genomic variation among rhesus macaques has implications for the use of this species as a model for studies of human health and disease, as well as for evolutionary population genomics. Whole-genome sequencing analysis of 133 rhesus macaques revealed more than 43.7 million single-nucleotide variants, including thousands predicted to alter protein sequences, transcript splicing, and transcription factor binding sites. Rhesus macaques exhibit 2.5-fold higher overall nucleotide diversity and slightly elevated putative functional variation compared with humans. This functional variation in macaques provides opportunities for analyses of coding and noncoding variation, and its cellular consequences. Despite modestly higher levels of nonsynonymous variation in the macaques, the estimated distribution of fitness effects and the ratio of nonsynonymous to synonymous variants suggest that purifying selection has had stronger effects in rhesus macaques than in humans. Demographic reconstructions indicate this species has experienced a consistently large but fluctuating population size. Overall, the results presented here provide new insights into the population genomics of nonhuman primates and expand genomic information directly relevant to primate models of human disease.

%B Genome Res %V 26 %P 1651-1662 %8 2016 Dec %G eng %N 12 %1 https://www.ncbi.nlm.nih.gov/pubmed/27934697?dopt=Abstract %R 10.1101/gr.204255.116 %0 Journal Article %J N Engl J Med %D 2010 %T Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. %A Lupski, James R %A Reid, Jeffrey G %A Gonzaga-Jauregui, Claudia %A Rio Deiros, David %A Chen, David C Y %A Nazareth, Lynne %A Bainbridge, Matthew %A Dinh, Huyen %A Jing, Chyn %A Wheeler, David A %A McGuire, Amy L %A Zhang, Feng %A Stankiewicz, Pawel %A Halperin, John J %A Yang, Chengyong %A Gehman, Curtis %A Guo, Danwei %A Irikat, Rola K %A Tom, Warren %A Fantin, Nick J %A Muzny, Donna M %A Gibbs, Richard A %K Adult %K Aged %K Aged, 80 and over %K Charcot-Marie-Tooth Disease %K Codon, Nonsense %K Female %K Genes, Recessive %K Genetic Association Studies %K Genome, Human %K Genotype %K Humans %K Male %K Middle Aged %K Mutation, Missense %K Pedigree %K Phenotype %K Polymorphism, Single Nucleotide %K Sequence Analysis, DNA %X

BACKGROUND: Whole-genome sequencing may revolutionize medical diagnostics through rapid identification of alleles that cause disease. However, even in cases with simple patterns of inheritance and unambiguous diagnoses, the relationship between disease phenotypes and their corresponding genetic changes can be complicated. Comprehensive diagnostic assays must therefore identify all possible DNA changes in each haplotype and determine which are responsible for the underlying disorder. The high number of rare, heterogeneous mutations present in all humans and the paucity of known functional variants in more than 90% of annotated genes make this challenge particularly difficult. Thus, the identification of the molecular basis of a genetic disease by means of whole-genome sequencing has remained elusive. We therefore aimed to assess the usefulness of human whole-genome sequencing for genetic diagnosis in a patient with Charcot-Marie-Tooth disease.

METHODS: We identified a family with a recessive form of Charcot-Marie-Tooth disease for which the genetic basis had not been identified. We sequenced the whole genome of the proband, identified all potential functional variants in genes likely to be related to the disease, and genotyped these variants in the affected family members.

RESULTS: We identified and validated compound, heterozygous, causative alleles in SH3TC2 (the SH3 domain and tetratricopeptide repeats 2 gene), involving two mutations, in the proband and in family members affected by Charcot-Marie-Tooth disease. Separate subclinical phenotypes segregated independently with each of the two mutations; heterozygous mutations confer susceptibility to neuropathy, including the carpal tunnel syndrome.

CONCLUSIONS: As shown in this study of a family with Charcot-Marie-Tooth disease, whole-genome sequencing can identify clinically relevant variants and provide diagnostic information to inform the care of patients.

%B N Engl J Med %V 362 %P 1181-91 %8 2010 Apr 01 %G eng %N 13 %1 https://www.ncbi.nlm.nih.gov/pubmed/20220177?dopt=Abstract %R 10.1056/NEJMoa0908094