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Genome Biology - Latest Articles
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The latest research articles published by Genome Biology
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Searching for SNPs with cloud computing
As DNA sequencing outpaces improvements in computer speed, there is a critical need to accelerate tasks like alignment and SNP calling. Crossbow is a cloud-computing software tool that combines the aligner Bowtie and the SNP caller SOAPsnp. Executing in parallel using Hadoop, Crossbow analyzes data comprising 38-fold coverage of the human genome in three hours using a 320-CPU cluster rented from a cloud computing service for about $85. Crossbow is available from http://bowtie-bio.sf.net/crossbow.
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COMIT: Identification of noncoding motifs under selection in coding sequences
Coding nucleotide sequences contain myriad functions independent of their encoded protein sequences. We present the COMIT algorithm to detect functional noncoding motifs in coding regions using sequence conservation, explicitly separating nucleotide from amino acid effects. COMIT concurs with diverse experimental datasets, including splicing enhancers, silencers, replication motifs, and microRNA targets, and predicts many novel functional motifs. Intriguingly, COMIT scores are well-correlated to scores uncalibrated for amino acids, suggesting that nucleotide motifs often override peptide-level constraints.
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Ancestry-related assortative mating in latino populations
Background:
While spouse correlations have been documented for numerous traits, no prior studies have assessed assortative mating for genetic ancestry in admixed populations.
Results:
Using 104 ancestry informative markers, we examined spouse correlations in genetic ancestry for Mexican spouse pairs recruited from Mexico City and the San Francisco Bay Area, and Puerto Rican spouse pairs recruited from Puerto Rico and New York City. In the Mexican pairs, we found strong spouse correlations for European and Native American ancestry, but no correlation in African ancestry. In the Puerto Rican pairs, we found significant spouse correlations for African ancestry and European ancestry but not Native American ancestry. Correlations were not attributable to variation in socioeconomic status or geographic heterogeneity. Past evidence of spouse correlation was also seen in the strong evidence of linkage disequilibrium between unlinked markers, which was accounted for in regression analysis by ancestral allele frequency difference at the pair of markers (European versus Native American for Mexicans, European versus African for Puerto Ricans). We also observed an excess of homozygosity at individual markers within the spouses, but this provided weaker evidence, as expected, of spouse correlation. Ancestry variance is predicted to decline in each generation, but less so under assortative mating. We...
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Biology inspires engineering
A report of the Cold Spring Harbor Laboratory/Wellcome Trust Meeting on Engineering Principles in Biology, Cambridge, UK, 14-16 October 2009.
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CTCF binding site classes exhibit distinct evolutionary, genomic, epigenomic and transcriptomic features
Background:
CTCF (CCCTC-binding factor) is an evolutionarily conserved zinc finger protein involved in diverse functions ranging from negative regulation of MYC, to chromatin insulation of the -globin gene cluster, to imprinting of the Igf2 locus. The eleven zinc fingers of CTCF are known to differentially contribute to the CTCF-DNA interaction at different binding sites. It is possible that the differences in CTCF-DNA conformation at different binding sites underlie CTCF's functional diversity. If so, the CTCF binding sites may belong to distinct classes, each compatible with a specific functional role.
Results:
We have classified approximately 26,000 CTCF binding sites in CD4+ T cells into three classes based on their similarity to the well-characterized CTCF DNA-binding motif. We have comprehensively characterized these three classes of CTCF sites with respect to several evolutionary, genomic, epigenomic, transcriptomic and functional features. We find that the low-occupancy sites tend to be cell type specific. Furthermore, while the high-occupancy sites associate with repressive histone marks and greater gene co-expression within a CTCF-flanked block, the low-occupancy sites associate with active histone marks and higher gene expression. We found that the low-occupancy sites have greater conservation in their flanking regions compared to high-occupancy sites. Interestingly, based on a novel class-conservation metric, we...
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BioGPS: an extensible and customizable portal for organizing and querying gene annotation resources
Online gene annotation resources are indispensable for analysis of genomics data. However, the landscape of these online resources is highly fragmented, and scientists often visit dozens of these sites for each gene in a candidate gene list. Here, we introduce BioGPS (http://biogps.gnf.org), a centralized gene portal for aggregating distributed gene annotation resources. Moreover, BioGPS embraces the principle of community intelligence, enabling any user to easily and directly contribute to the BioGPS platform.
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Differential binding and co-binding pattern of FOXA1 and FOXA3 and their relation to H3K4me3 in HepG2 cells revealed by ChIP-seq
Background:
The forkhead box/winged helix family members FOXA1, FOXA2, and FOXA3, are of high importance in development and specification of the hepatic linage and the continued expression of liver-specific genes.
Results:
Here, we present a genome-wide location analysis of FOXA1 and FOXA3 binding sites in HepG2 cells through chromatin immunoprecipitation with detection by sequencing (ChIP-seq) studies and compare these with our previous results on FOXA2. We found that these factors often bind close to each other in different combinations and consecutive immunoprecipitation of chromatin for one and then a second factor (ChIP-reChIP) shows that this occurs in the same cell and on the same DNA molecule, suggestive of molecular interactions. Using co-immunoprecipitation, we further show that FOXA2 interacts with both FOXA1 and FOXA3 in vivo, while FOXA1 and FOXA3 do not appear to interact. Additionally, we detected diverse patterns of trimethylation of lysine 4 on histone H3 (H3K4me3) at transcriptional start sites and directionality of this modification at FOXA binding sites. Using the sequence reads at polymorphic positions, we were able to predict allele specific binding for FOXA1, FOXA3, and H3K4me3. Finally, several SNPs associated with diseases and quantitative traits were located in the enriched regions.
Conclusions:
We find that ChIP-seq can be used not...
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Genome Alteration Print (GAP): a tool to visualize and mine complex cancer genomic profiles obtained by SNP arrays
We describe a method for automatic detection of absolute segmental copy numbers and genotype status in complex cancer genome profiles measured by single nucleotide polymorphism (SNP) arrays. The method is based on pattern recognition of segmented and smoothed copy number and allelic imbalance profiles. Assignments were verified by DNA indexes of primary tumors and karyotypes of cell lines. The method performs well even for poor quality data, low tumor content, and highly rearranged tumor genomes.
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Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis
Background:
Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, a Gram-negative bacillus classified by the National Institute of Allergy and Infectious Diseases (NIAID) as a category B priority agent. Septicemia is the most common presentation of the disease with a 40% mortality rate even with appropriate treatments. Better diagnostic tests are therefore needed to improve therapeutic efficacy and survival rates.
Results:
We have used microarray technology to generate genome-wide transcriptional profiles (>48,000 transcripts) from the whole blood of patients with septicemic melioidosis (n=32), patients with sepsis caused by other pathogens (n=31), and uninfected controls (n=29). Unsupervised analyses demonstrated the existence of a whole blood transcriptional signature distinguishing patients with sepsis from control subjects. The majority of changes observed were common to both septicemic melioidosis and sepsis caused by other infections, including genes related to inflammation, interferon-related genes, neutrophils, cytotoxic cells, and T-cells. Finally, class prediction analysis identified a 37 transcript candidate diagnostic signature that distinguished melioidosis from sepsis caused by other organisms with 100% accuracy in a training set. This finding was confirmed in 2 independent validation sets, which gave high prediction accuracies of 78% and 80% respectively. This signature was significantly enriched in genes coding for products involved in the...
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Construction of a high-resolution genetic linkage map and comparative genome analysis for a reef-building coral Acropora millepora
Background:
Worldwide coral reefs are in decline due to a range of anthropogenic disturbances, and are now also under threat from global climate change. Virtually nothing is currently known about the genetic factors that might determine whether corals adapt to the changing climate or continue to decline. Quantitative genetics studies aiming to identify the adaptively important genomic loci will require a high-resolution genetic linkage map. The phylogenetic position of corals also suggests important applications for a coral genetic map in studies of ancestral metazoan genome architecture.
Results:
We constructed a high-resolution genetic linkage map for the reef-building coral Acropora millepora, the first genetic map reported for any coral, or any non-Bilaterian animal. More than 500 single nucleotide polymorphism (SNP) markers were developed, most of which are transferable in populations from Orpheus Island and Great Keppel Island. The map contains 429 markers (393 gene-based SNPs and 36 microsatellites) distributed in 14 linkage groups, and spans 1493 cM with an average marker interval of 3.4 cM. Sex differences in recombination were observed in a few linkage groups, which may be caused by haploid selection. Comparison of the coral map with other metazoan genomes (human, nematode, fly, anemone and placozoan) revealed synteny regions.
Conclusions:
Our study develops a...
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