Research

Overview

     Research in biology and medicine has been greatly transformed in the last decade, specially by the generation, processing and analysis of large datasets. Part of this transformation is the result of large DNA sequencing projects – such as the Human Genome Project - and, more recently, the improvement in high-throughput sequencing technologies. A decisive factor in this transformation however, was the evolution if computational power and the development of new fields such as bioinformatics (or Computational Biology), which integrate computational sciences with biological areas. Presently there are countless groups working on bioinformatics and ours is one of them. The Bioinformatics Group at the IEP-HSL was created recently and our main goal is to produce high-quality research in the field of bioinformatics, biology and medicine.

 

Research interests

     Specifically, we focus on Genomics (Genomics), transcriptomics, and generating computational webtools, all of it applied mainly to cancer research. We currently have projects in all of these lines, which comprehend mostly: I) the study of simple and complex structural variations in normal and tumor genomes; ii) the study of post-transcriptional events; iii) the study of differentially expressed genes, related or not to pathological states; iv) the development of computational tools related to analysis of non coding genes. Below you can find a more detailed description of some of our projects:

 

1 - Study of simple and complex variations in normal and pathological genomes.

 

     Genomic variations occur in every living being and are considered by many as the basis for natural selection. These variations account for the differences between individuals of the same species (in average we present 0.1% of genomic difference with relation to any other human being for example). These variations however, are also responsible for the development or a predisposition (weak or strong) to some diseases. Somatic mutations in specific genes and chromosomal rearrangements give origin to most cases of human cancers. The field of Oncobiology is going through a revolution due to low sequencing costs and a high-throughput generation of data. Our group is interested in the study of variations, both simple and complex, in normal genomes and pathological states, especially cancer. Thus, we use computational tools and large scale DNA sequencing focused on relevant biological questions.

 

2 - Study of post-transcriptional events.

 

     Part of the complexity of our species is consequence of the processing of RNAs that occurs after gene transcription. Alternative splicing , for example occurs in ~95% of human multi-exonic genes. Another frequent phenomenon, called alternative polyadenylation , occurs in ~50% of our species coding genes. These processes are not exclusive to Homo sapiens (they are present in nearly all eukaryotes) and occur in a different manner in different tissues and pathological states. We now know that alternative splicing is involved in 15% of our genetic diseases and that alternative polyadenylation can be related to different types of tumors. These phenomena have been systematically explored since the beginning of genomic studies (especially the human genome) and benefit from the current technologies for sequencing, analysis and functional studies in large scale. Our group is also very interested in the study of alternative splicing and polyadenylation in the different tissues and in different types of tumor, for example.

 

3 - Study of differentially expressed genes in physiological or pathological states.

 

     The control of gene expression is essential to all organisms, development stages and normal physiological conditions. This is partly consequence if the differential gene expression present amongst different cell types, tissues and organs in a multi-cellular organism. However, deregulation of this fine control is related to diverse pathologies, including cancer. Tumor cells have, in general, distinct gene expression profiles than their counterpart normal tissues. Potentially, these genes can be used to classify tumors in subtypes, predict some of its characteristics (aggressiveness and invasion capacity, for example) and disease evolution. Our group is interested in the study of differential gene expression in tumors (especially colon, rectal and breast tumors). We are also interested in the study of differentially expressed genes in developmental stages, tissues and distinct organs.

 

4 - Development of computational tools related to miRNA analysis.

 

     miRNAs are short molecules, 22nt in average, that bind to target regions (usually 3'UTR) of coding mRNAs and initiate mechanisms of translational repression and/or mRNA decay. There are ~1500 miRNA genes already identified in the human genome and it is stipulated that these miRNAs have as target over ~60% of our protein coding genes. We also know that many of these miRNAs are located in the introns of coding genes (>50%) and that this may have important functional implications. Our group is greatly interested in exploring and developing tools to study genomics, transcriptomics and integrate diverse information related to miRNAs, especially intragenic miRNAs (see miRIAD).

 

     In all our work we rely on a computational environment based on Linux, using many programming languages (Perl, Python, PHP, R and Shell Script) and interaction with MySQL database. All data we produce and all our applications/programs/scripts are under a GPL license.

 

Summary

     The Bioinformatics Group at the IEP – HSL aims to systematically integrate computation and biology with the purpose of exploring relevant scientific questions and generating basic and applied knowledge in the fields of bioinformatics, biology and medicine.