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High-throughput genome-wide analyses

(a) Genome-wide molecular analyses (transcriptional profiling, epigenetic regulation, and signaling) in selected cell types.

Combined analyses of expression and signaling will reveal in detail the state of activation and the expression programs activated in relevant cell subsets that predict their functional activities. Excessive, polarized or unusual functions of particular cell types are likely to underlie immune pathology.  The center can assist with genome-wide surveys of epigenetic and transcriptional signatures. This includes expression profiling using arrays and RNA sequencing, chromatin marks, DNA methylation, etc.

Additional studies that can be performed include:

RNA sequencing in purified populations: Chip arrays or additional data from RNA sequencing (unannotated genes, spliced isoforms and non-coding RNAs) allow discovery of pathways and network analysis within specific cell subsets relevant to disease states.

Epigenetic profiling: Methylation, DNase hypersensitivity and histone mark measurements complement expression profiling data to understand how gene expression patterns are controlled.

Single cell RNA-seq: Although this technique is just coming on line, the ability to perform single cell expression analysis will now enable a detailed molecular assessment of individual cells from biopsies of involved tissues. The ability to compare expression programs from immune cells from relevant tissues with peripheral blood of the same patient (at the same time) promises to reveal human immune aberrations relevant to disease previously not possible.

(b) Inherited DNA variation.

High-throughput genotyping and sequencing have revolutionized our understanding of inherited variation in the human genome. It is now possible to genotype or sequence the entire human genome in a single patient at an affordable cost. We work closely with other genome scientists at the Broad Institute and elsewhere to ensure that we are utilizing the most up-to-date genomic technologies available anywhere in the world. The actual sequencing and genotyping itself can be done either at genome centers within industry or academic laboratories. More importantly, our team has the expertise to analyze and integrate genetic data from these studies in the context of human disease. Through collaboration with clinicians in various specialties and in some cases across institutions, we are able to interpret genetic data with regard to other large-scale genomic data sets such as genome-wide association studies (GWAS) and whole genome sequencing projects.

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