Project description:The study is intended to collect specimens to support the application of genome analysis technologies, including large-scale genome sequencing. This study will ultimately provide cancer researchers with specimens that they can use to develop comprehensive catalogs of genomic information on at least 50 types of human cancer. The study will create a resource available to the worldwide research community that could be used to identify and accelerate the development of new diagnostic and prognostic markers, new targets for pharmaceutical interventions, and new cancer prevention and treatment strategies. This study will be a competitive enrollment study conducted at multiple institutions.
Project description:The Oxford Nanopore technology has a great potential for the analysis of genome methylation, including full-genome methylome profiling. However, there are certain issues while identifying methylation motif sequences caused by low sensitivity of the currently available motif enrichment algorithms. Here, we present Snapper, a new highly-sensitive approach to extract methylation motif sequences based on a greedy motif selection algorithm. Snapper has shown higher enrichment sensitivity compared with the MEME tool coupled with Tombo or Nanodisco instruments, which was demonstrated on H. pylori strain J99 studied earlier using the PacBio technology. In addition, we used Snapper to characterize the total methylome of a new H.pylori strain A45. The analysis revealed the presence of at least 4 methylation sites that have not been described for H. pylori earlier. We experimentally confirmed a new CCAG-specific methyltransferase and indirectly inferred a new CCAAK-specific methyltransferase.
Project description:Here, we report genome sequences of the two bioluminescent S. aureus strains Xen31 and Xen36, obtained from PerkinElmer (#119242 and #119243, respectively). Xen31 was derived from the parental MRSA strain ATCC33591, a clinical strain isolated at Elmhurst Hospital in New York City. Xen36 was derived from parental strain ATCC 49525, a clinical isolate from a bacteremic patient. A copy of the modified luxABCDE operon from Photorhadbus luminescenst is integrated in the chromosome of Xen31 and in a native plasmid of Xen36.
Project description:Data from multiple high throughput technologies such as RNA sequencing (RNA-Seq) and protein mass spectrometry (MS/MS) are often used to assist in predicting eukaryote genome features such as genes, splice variants, and single nucleotide variants (SNVs). The genomes of parasitic nematodes causing neglected tropical diseases are often poorly annotated. Angiostrongylus costaricensis, a nematode that causes an intestinal inflammatory disease known as abdominal angiostrongyliasis (AA), is one example. Currently, no drugs or treatments are available for AA, a public health problem in Latin America, especially in Costa Rica and Brazil. The available genome of A. costaricensis, specific to the Costa Rica strain, is a draft version not supported by transcript- or protein-level evidence. This study used RNA-Seq and MS/MS data to perform an in-depth annotation of the A. costaricensis genome. Our prediction supplemented the reference annotation with a) novel coding and non-coding genes; b) pieces of evidence of alternative splicing generating new proteoforms; c) a list of SNVs specific to the Brazilian strain (Crissiumal). To the best of our knowledge, this is the first time that a multi-omics approach has been used to improve the genome annotation of a parasitic nematode. We hope this supplemented genome annotation can assist the future development of drugs to treat AA caused by either Brazil strain (Crissiumal) or Costa Rica strain.
Project description:Streptococcus pneumoniae (pneumococcus) is a major human respiratory pathogen and the leading cause of bacterial pneumonia worldwide. Small regulatory RNAs (sRNAs), which often act by post-transcriptionally regulating gene expression, have been shown to be crucial for the virulence of S. pneumoniae and other bacterial pathogens. Over 170 putative sRNAs have been identified in S. pneumoniae TIGR4 strain (serotype 4) through transcriptomic studies, and a subset of these sRNAs have been further implicated in regulating pneumococcal pathogenesis. However, there was little overlap in the sRNAs identified among these studies, which indicated that the approaches used for sRNA identification were not sufficiently sensitive and robust and that there were likely many more undiscovered sRNAs encoded in the S. pneumoniae genome. Here, we sought to comprehensively identify sRNAs in Avery's virulent S. pneumoniae strain D39 using two independent RNA-seq based approaches. We developed an unbiased method for identifying novel sRNAs from bacterial RNA-seq data and have further tested the specificity of our analysis program towards identifying sRNAs encoded by both strains D39 and TIGR4. Interestingly, the genes for 15% of the putative sRNAs identified in strain TIGR4 including ones previously implicated in virulence were not present in strain D39 genome suggesting that the differences in sRNA repertoires between these two serotypes may contribute to their strain-specific virulence properties. Finally, this study has identified 67 new sRNA candidates in strain D39, 28 out of which have been further validated, raising the total number of sRNAs that have been identified in strain D39 to 112.
Project description:The rapid rise in antibiotic-resistance of microbial pathogens has brought the attention to new, heterologous approaches to better exploit the vast repertoire of biosynthetic gene clusters in Actinobacteria genomes and the large number of potentially novel bioactive compounds encoded in these. To enable and optimize production of these compounds, a better understanding of -among others- the interplay between primary and secondary metabolism in the selected suitable heterologous production hosts is needed, in our case the model Streptomycete Streptomyces coelicolor. In this study, a genome-scale metabolic model is reconstructed based on several previous metabolic models and refined by including experimental data, in particular proteome data. This new consensus model provides not only a valuable and more accurate mathematical representation to predict steady-state flux distributions in this strain, but also provides a new framework for interpretation and integration of different 'omics' data by the Streptomyces research community for improved strain-specific systems-scale knowledge to be used in targeted strain development, e.g. for efficient new antibiotics production.
Project description:Interventions: Gold Standard:the pathological biopsy results after resection of colorectal mass;Index test:elasticity score; strain ratio
Primary outcome(s): elasticity score;strain ratio;the pathological biopsy results after resection of colorectal mass
Study Design: Diagnostic test for accuracy
Project description:We employed a proteogenomics workflow to identify microproteins encoded by small Open Reading Frames (ORFs) in the genome of Mycobacterium smegmatis strain mc²155.