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 and splicing 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 trasncriptomic changes in both coding and non-coding genes are associated with different human phenotypes and diseases. The group participates in different international consortia such as the Genotype-Tissue Expression Project (GTEx) and the single-cell eQTLGen Consortium (sc-eQTLGen).

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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.

Single-cell transcriptomics and aging

Aging is nearly a universal process affecting all tissues. Despite its constancy in our lives, aging remains mysterious at a fundamental level. Primary hallmarks of aging include cell-autonomous changes linked to epigenetic alterations, genomic instability, telomere attrition, and loss of proteostasis (protein homeostasis), which are followed by antagonistic responses such as deregulated nutrient sensing, altered mitochondrial function, and cellular senescence. Whether these hallmarks of aging occur across different tissues, and what are the aging changes driven by expression, splicing or cell type composition remains poorly understood. Studies using bulk RNA-seq samples have reported that age-related gene expression and splicing patterns notably vary in a tissue-wise fashion.  However, since bulk samples of heterogeneous mixtures (i.e., tissues) only represent averaged expression levels, these findings could be confounded by differences in cell type proportions. We use single-cell RNA-sequencing (scRNA-seq) technologies to disentangle the age-related gene expression changes to the cellular composition variation across tissues and individuals. Ultimately, this information can promote the development of personalized medicine, as well as understanding the biological mechanism of the aging process.

Group News

Raquel Garcia-Perez is awarded the Juan de la Cierva Incorporacion fellowship (August 2021)

Erola Pairo obtained a STARS-cofund postdoctoral grant to join the lab (October 2020)

Marta Melé is awarded the Plan Nacional Project "The anatomy of the human transcriptome in health and disease" (June 2020)

Marta Melé is awarded a Fundació La Marató Project "Epigenetic Characterization of Cholangiocarcinomas" together with Sandra Peiró (VHIO) (December 2019)

Marta Melé is awarded the L'Oréal-Unesco for Women in Science Award

Kaia Mattioli is awarded Severo Ochoa mobility grant to visit our lab at BSC