Transcriptomics and Functional Genomics Lab (TFGL)

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The Transcriptomics and Functional Genomics Lab is interested in understanding how the information encoded in our genome determines gene expression variation across individuals and tissues. To address this, we use a combination of cutting-edge computational analyses, next generation sequencing, and high-throughput functional assays. Our goal is to perform integrative analyses of “-omics” data to ultimately understand how expression changes in both coding and non-coding genes are associated with disease.

Objectives

Personalized transcriptomics

Transcriptional regulation plays a central role in cellular identity and tissue organization. Thus, the study of the regulation of the human transcriptome is crucial to understand how disruption of this regulation can lead to disease. Our lab takes advantage of large-scale transcriptomics and epigenomics datasets to systematically study the relationship between gene expression and disease states across many individuals simultaneously. For example, we are involved GTEx project and thus, we have unique access to human transcriptomics data across hundreds of human individuals and tissues simultaneously. Rather than focusing on specific tissues, we try to understand how the transcriptome at the organism level varies under certain conditions or phenotypic states. We pay special attention to the role that long non-coding RNAs play in these processes and how they differ from other gene classes such as protein coding genes. We also focus on related biological processes such as splicing, RNA decay, and differences in cell-type composition, either on a gene-by-gene basis or using a networks approach. Related publication: Melé M, et al. Science. 2015.

Additionally, through collaborations we have access to unique transcriptomics datasets, related to specific diseases such as Ebola, through a collaboration with Pardis Sabeti (Broad Institute of Harvard and MIT), and cancer, through Sandra Peiró’s group (VHIO, Barcelona).

Characterization of non-coding regulatory elements

Genome wide association studies have identified hundreds of genomic loci harboring common genetic variants associated with disease susceptibility. However, most of these loci are located in non-coding regions of the genome and, therefore, remain largely uncharacterized. Our lab combines cutting-edge computational analyses and high-throughput functional assays to systematically study non-coding regulatory elements such as enhancers, promoters, and silencers. We take advantage of the recent development of massively parallel reporter assays (MPRA) to analyze tens of thousands of individual DNA oligonucleotides simultaneously. The ultimate goal is to understand how disruption of these non-coding regulatory elements by specific genetic variants mediates differences in disease susceptibility between individuals. Related publication: Mattioli KM et al. Genome Research 2018.

We plan on performing MPRA experiments in house very soon but we are also collaborating with the Maass lab (University of Toronto, Canada) to perform MPRA to answer questions related with specific diseases such as breast cancer and hypertension.