Human Genetics and Microbiome Core

Overview

This Core continues to bring a variety of cutting-edge techniques in genetics/genomics and microbiome research as well as computational resources. This Core provides current and emerging technologies, pursues robust performance at the highest quality standards, and is committed to drive development toward future needs.

Core services are broadly divided between training and education, access to tools for molecular biology and ‘omics data generation, and computational resources for data analysis. The Core also introduced a comprehensive biobank of human gut bacteria, the Broad Institute Open-Biome Microbiome Library, that contains 7,758 bcaterial isolates with 3,632 paired genome sequences covering most of the phylogenetic diversity found in the gut.

In addition to building and supporting a vibrant community around a common interest, the leadership’s involvement in large-scale, international research projects also results in early access to emerging results. One such project is an ongoing effort to aggregate genomic sequencing datasets into the IBD Exomes Browser, which will aid investigations into genetic causes of IBD. These and other Center data resources will be accessible through the IBD Data Science Commons, a new resource within the Core. The IBD Data Science Commons will provide CSIBD members with access to a secure cloud-based platform for management and computational analysis of large scale genetic and microbiome datasets.

Objectives

1. Facilitate the application of advanced experimental platforms for genetics, genomics and high-throughput data analysis to discovery efforts relevant to IBD.
2. Provide a centralized facility and personnel for performing state-of-the-art recombinant and PCR-based DNA procedures and provide cost-effective and high-quality molecular biology reagents and services including reporter gene constructs, expression plasmids, viral vectors, real-time PCR, mutagenesis, expertise for differential mRNA display analysis, CRISPR reagents, bulk RNA-seq library preparation, Mi-seq next generation sequencers, and facilitated access to bioinformatics support.
3. Provide a resource for disseminating a wide range of molecular biology, genetic and bioinformatics technologies.
4. Provide an end-to-end sampling and multi’omic profiling system for the host and microbiota in IBD and gastrointestinal disease.
5. Provide computational resources to analyze and interpret the microbiome in health and gastrointestinal disease.
6. Develop cutting-edge solutions in microbiome research that will drive therapeutic discovery.

Services

• Consultation and training. Central to all services are formal and informal end-to-end consultations on grant proposal development, experimental design, data generation, bioinformatics analysis and data interpretation. A variety of training opportunities and workshops are also offered to aid investigators in study design and data analysis from genetics-, genomics- and microbiome-based projects. For experimental work, full access to protocols and reagents for sophisticated molecular biology and microbiome-based approaches is provided.

• Bioinformatics support. A team of bioinformaticists and software developers with in-depth expertise are available within the Core to provide collaborative capacity for data analysis. For human genetics, this includes handling RNA-Seq, pathway reconstruction tools, and state-of-the-art pipelines for genome annotation, exome analysis, and interpretation. For microbiome data, this includes analysis of taxonomic and functional composition using tools available from several platforms. 

• Tools for molecular biology:

  • Routine molecular biology tools including PCR, DNA procedures, oligonucleotide synthesis, real-time qPCR, and microsatellite fragment analysis
  • Resource-intensive methodologies including cDNA library prep and siRNA/shRNA and CRISPR screens
  • Genotyping and DNA fragment analysis
  • CRISPR amplicon sequencing
  • Complete plasmid and RNA sequencing using next-generation sequencing

  • Repository of BACs, plasmids, libraries, RNA samples and probes

  • Gene profiling services by deep sequencing

• Microbiome data generation: 

  • Coordinated sample collection from patients, de-identified receipt, and sample handling (portioning and long-term storage)

  • High-throughput DNA/RNA extraction from multiple sample types (bacterial culture, stool, and biopsy)

  • Metabolite profiling of microbiome samples

  • High-throughput 16S rRNA sequencing

  • DNA library construction and deep shotgun sequencing

  • RNA and RNAtag-Seq library construction, rRNA depletion, and deep shotgun sequencing