Wobbly possum disease (WPD) is a fatal neurological disease of the Australian brushtail possum. Using next-generation sequencing, researchers isolated a partial genomic sequence of the putative WPD virus from tissues of affected animals. Further analysis identified the candidate virus as a novel nidovirus.
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Dunowska M, Biggs PJ, Zheng T, Perrott MR
Identification of a novel nidovirus associated with a neurological disease of the Australian brushtail possum (Trichosurus vulpecula) Vet Microbiol.
Tumor heterogeneity presents a challenge for inferring clonal evolution and driver gene identification. To address this issue, researchers developed a high-throughput whole-genome single-cell sequencing method on the HiSeq2000 system. Using this method, it was determined that 58 out of 90 cells from a JAK2-negative myeloproliferative neoplasm patient represented a monoclonal evolution, allowing initial characterization of the disease-related genetic architecture at the single-cell nucleotide level.
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Hou Y, Song L, Zhu P, Zhang B, Tao Y, et al.
Single-cell exome sequencing and monoclonal evolution of a JAK2-negative myeloproliferative neoplasm Cell
Clear cell renal cell carcinoma (ccRCC) has few mutations shared between patients. To further understand intratumoral, single-cell exome sequencing on a ccRCC tumor was carried out on a HiSeq2000 system. Results revealed that ccRCC is more genetically complex than previously thought. This method provides information that may lead to development of more effective cellular targeted therapies.
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Xu X, Hou Y, Yin X, Bao L, Tang A, et al.
Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor Cell
Researchers performed the same amplicon sequencing protocol with the HiSeq2000 and MiSeq systems on 24 microbial communities from host-associated and free-living environments. Data generated by both systems differed only in scale, with technical replicates and amplicon sequencing of different regions yielding the same biological conclusions. The study demonstrates that while the HiSeq can perform low-cost massively parallel sequencing for large projects, the MiSeq can generate comparable data for smaller projects where turnaround time is more critical.
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Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J, et al.
Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms ISME J
Next-generation whole-genome sequencing of representative strains of C. trachomatis from trachoma and lymphogranuloma venereum (LGV) biovars identified extensive recombination in the ompA region traditionally used to classify Chlamydia. A detailed phylogeny demonstrated that the prediction of phylogenetic structure using ompA is misleading, with genetic exchange manifesting itself in ocular, urogenital, and LGV C. trachomatis strains, including the epidemic LGV serotype L2b.
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Harris SR, Clarke IN, Seth‐Smith HM, Solomon AW, Cutcliffe LT, et al.
Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing Nat Genet
The mammalian target of rapamycin (mTOR) kinase is a key regulator of protein synthesis that couples nutrient sensing to cell growth and cancer. However, downstream translationally regulated nodes of gene expression that may direct cancer development are poorly characterized. Ribosome profiling using next-generation sequencing revealed specialized translation of the prostate cancer genome by oncogenic mTOR signalling, revealing a specific repertoire of genes involved in cell proliferation, metabolism, and invasion.
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Hseih AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, et al.
The translational landscape of mTOR signalling steers cancer initiation and metastasis Nature
14-3-3 proteins regulate a range of cellular functions, and altered expression is associated with development and progression of cancer. Using cytogenetics and a whole-transcriptome sequencing approach, the authors identified a t(10;17) genomic rearrangement, leading to fusion between 14-3-3ε and either of two nearly identical FAM22 family members that is highly recurrent in aggressive endometrial stromal sarcoma (ESS). These discoveries reveal models for characterizing aberrant 14-3-3 oncogenic functions.
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Lee CH, Ou WB, Mariño-Enriquez A, Zhu M, Mayeda M, et al.
14‐3‐3 fusion oncogenes in high‐grade endometrial stromal sarcoma Proc Natl Acad Sci USA
Researchers performed whole-genome and transcriptome sequencing on primary and metastatic tissues collected from an aggressive prostate tumor. Despite the presence of a homogeneous cell type, analysis of the transcriptome and genome revealed a hybrid tumor expressing both luminal and neuroendocrine gene signatures, representing a novel and highly aggressive case of prostate cancer. This result demonstrates the value of integrated genome, exome, and transcriptome sequences for molecular pathology and personalized oncology.
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Wu C, Wyatt AW, Lapuk AV, McPherson A, McConeghy BJ
Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer J Pathol
High-throughput sequencing was used to analyze gene matrices associated with specific disease phenotypes to screen for potential small molecules inhibitors. By applying this multi-target method to hormone-refractory prostate cancer, Peruvoside, a cardiac glycoside capable of inhibiting cancer cells without triggering severe cytotoxicity, was identified. This approach connects pathways of phenotypic response to the molecular mechanism of drug action, offering a unique pathway-centric strategy for drug discovery.
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Li H, Zhou H, Wang D, Qiu J, Zhou Y, et al.
Versatile pathway-centric approach based on high-throughput sequencing to anticancer drug discovery Proc Natl Acad Sci USA
Using paired-end sequencing, tens of thousands of short extrachromosomal circular DNAs (microDNA) in mouse tissues, and mouse and human cell lines were identified. These 200–400 bp microDNAs derived from unique non-repetitive sequence, are enriched in the 5' untranslated regions of genes, exons, and CpG islands. These newly identified entities may explain microdeletions observed in different genomic loci, resulting from their excision.
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Shibata Y, Kumar P, Layer R, Willcox S, Gagan JR, et al.
Extrachromosomal microDNAs and chromosomal microdeletions in normal tissues Science
