Somatic mutations can affect key domains of cancer genes. These mutations can be detected through ultra-deep targeted sequencing (UDT-Seq). However, current methods are difficult to adapt to a clinical environment. Using the MiSeq system to target 71kb of mutational hotspots in 42 cancer genes in 6 tumor samples, the authors streamlined the workflow and increased detection sensitivity and specificity for low-prevalence mutations.
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Harismendy O, Schwab EB, Bao L, Olson J, Rozenzhak S, et al.
Detection of low prevalence somatic mutations in solid tumors with ultra-deep targeted sequencing Genome Biol
cDNA libraries made from individual, electrophysiologically identified warm sensitive neurons (WSN) were analyzed initially by microarray, followed by Illumina sequencing. cDNAs encoding the GABA biosynthetic enzyme Gad1, adrenomedullin, galanin, prodynorphin, somatostatin, and tachykinin were found. Analysis revealed heterogeneity within WSN transcriptomes, suggesting strong epigenetic influence.
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Eberwine J, Bartfai T
Single cell transcriptomics of hypothalamic warm sensitive neurons that control core body temperature and fever response signaling asymmetry and an extension of chemical neuroanatomy Pharmacol Ther
Ribosome profiling (deep sequencing of ribosome-protected mRNA fragments) was used to produce genome-wide maps of protein synthesis. Data analysis revealed thousands of strong pause sites and unannotated translation products, including amino-terminal extensions and truncations and upstream open reading frames with regulatory potential. In addition, a new class of short, polycistronic ribosome-associated coding RNAs (sprcRNAs) that encode small proteins was uncovered, demonstrating a higher level of complexity to mammalian proteomes.
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Ingolia NT, Lareau LF, Weissman JS
Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes Cell
Analysis of bacterial evolution has been hampered by experimental cultures that do not accurately reflect what is occurring in vivo. Scientists developed the morbidostat, a microbial selection device for the real-time analysis of bacterial evolution, testing E. coli under antibiotic selection. The Genome Analyzer was used to perform whole-genome sequencing of the resulting isogenic clones, identifying multiple resistance pathways. This is the first study to elucidate the ordered adaptive pathways that lead to bacterial antibiotic resistance.
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Toprak E, Veres A, Michel JB, Chait R, Hartl Dl, et al.
Evolutionary paths to antibiotic resistance under dynamically sustained drug selection Nat Genet
To understand the relationship between the amount of sequence data and the callable portion of the genome necessary for confident genotype calling, the Genome Analyzer and HiSeq 2000 systems were used to perform whole-genome sequencing of a patient blood sample. Using mapping quality and genotype confidence filters, an average mapped depth of 50× was required to make confident genotype calls for > 94% of the genome and > 80% of the coding exome, 20× higher than the current recommendation.
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Ajay SS, Parker SC, Abaan HO, Fajardo KV, Margulies EH
Accurate and comprehensive sequencing of personal genomes Genome Res
Using sequencing and array-based genotyping, researchers re-examined unexplained heritability in five loci associated with low-density lipoprotein cholesterol (LDL-C). Through this approach, heritability estimates of LDL-C increased from 3.1% to 6.5%, demonstrating that sequencing efforts paired with large-scale genotyping will increase estimates of complex trait heritability explained by known loci.
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Sanna S, Li B, Mulas A, Sidore C, Kang HM, et. Al
Fine mapping of five loci associated with low-density lipoprotein cholesterol detects variants that double the explained heritability PLoS
The Illumina Genome Analyzer (GAII) and a long-read technology were used for SNPs discovery in the European Hake muscle transcriptome. Despite shorter sequence lengths, the GAII data showed similar assay conversion rates and percentages of polymorphic loci, demonstrating suitability of short reads for large-scale identification of SNPs in transcribed regions of non-model species.
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Milano I, Massimilian B, Panitz F, Ogden R, Rasmu NO, et. al
High-throughput approaches for SNP discovery in the transcriptome of the European Hake PLoS
The Genome Analyzer was used for whole-genome and exome sequencing of leukemia cells from chronic lymphocytic leukemia (CLL) patients, identifying several established and unknown gene mutations. The spliceosome component SF3B1 was mutated at significant frequency, and showed striking associations with other CLL prognostic markers. These data reinforce the theory that combinations of somatic mutations may act in concert to spur cancer progression.
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Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, et al.
SF3B1 and other novel cancer genes in chronic lymphocytic leukemia New Engl J Med
By comparing non-overlapping paired-end and single reads from the Genome Analyzer, the authors show that accurate phylogenetic relationships and diversity analyses can be determined from microbiome and environmental samples. This may be a particularly useful method for surveying the V4 region of 16S rRNA, which is used in many metagenomics studies.
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Werner JJ, Zhou D, Caporaso JG, Knight R, Angenent LT
Comparison of Illumina paired-end and single-direction sequencing for microbial 16S rRNA gene amplicon surveys ISME J
