PostDoc Project: SFRH/BPD/96890/2013

Development of software tools for the prediction of cellular fate in stem cell differentiation


Summary

Cellular reprogramming has become a major research focus in biomedicine with great potential, as it might enable the establishment of new therapies in regenerative medicine. Such stem cell-based therapies are of rapidly growing relevance, especially for the aging population in Western countries. However, the underlying process is highly complex and obtaining specific cell lineages remains challenging. Despite recent progresses, there exists a prominent need for dedicated resources to assist the rationale design and optimization of experimental protocols for cellular reprogramming.

The objective of this project is to develop web-based software tools that can help biomedical researchers in the identification of genes whose expression has to be modified to guide stem cell differentiation into a specific lineage. So far StemCellNet, a web-server for network-based investigations of processes associated with stem cell maintenance and differentiation has been implemented. StemCellNet provides access to over 100 000 molecular interactions detected in stem cells and their integration with complementary data. In addition another publicly available web-server termed StemChecker , for detection of stem cell signatures in gene sets provided by the user, has also been developed. This tool comprises a large number of curated gene sets associated with stemness and can help researchers to gain novel insights in stemness related process not only in stem cell biology, but also human diseases such as cancer and neurodegenerative disorders. Both tools are designed to facilitate the query and analysis of stem cell-relevant data in an intuitive manner, while providing state-of-the-art tools for customized investigations.

Future applications will also be capable of suggesting drugs to target the identified genes (see also the review in Frontiers in Genetics ) and be linked to a database that integrates information from various sources. An important input will be data and models generated in the "Alternative splicing and its impact on molecular networks during stem cell differentiation project", funded by FCT (PTDC/BIA- GEN/116519/2010).


Postdoc Fellowship

José Pedro B. G. P. Pinto, CBMR, Universidade do Algarve, Portugal

Supervisors

Matthias Futschik, Universidade do Algarve, Portugal

Jose Brangança, Universidade do Algarve, Portugal

Publications

José P. Pinto, Ravi K. Kalathur, Daniel V. Oliveira, Tânia Barata, Rui S. R. Machado, Susana Machado, Ivette Pacheco-Leyva, Isabel Duarte and Matthias E. Futschik (2015). StemChecker: a web-based tool to discover and explore stemness signatures in gene sets, Nucleic Acids Research 43 (W1): W72-W77 (pdf + html)

José P. Pinto, Rui Machado, Joana Gonçalves Xavier and Matthias E. Futschik (2014) Targeting molecular networks for drug research. Frontiers in Genetics 5:160 (pdf + html )

José P. Pinto, Ravi K.R. Kalathur, Rui S. R. Machado, Joana M. Xavier, José Bragança, and Matthias E. Futschik (2014) StemCellNet: an interactive platform for network-oriented investigations in stem cell biology. Nucleic Acids Research 42:W154-W160. (pdf+html)



Presentations

    J Pinto, Machado, R Kalathur, DV Oliveira, T Barata, R Machado, S Machado, I Pacheco-Leyva, I Duarte, M Futschik (2016) StemChecker: a web-based tool to discover and explore stemness signatures in gene sets. Bioinformatics Open Days, Braga, Portugal

    JP Pinto, R Kalathur, RS Machado, J Xavier, J Bragança & ME Futschik (2015) StemCellNet: an interactive platform for network -oriented investigations in stem cell biology.9th International Meeting of the Portuguese society for Stem cells and Cell therapies. Oeiras. Portugal.

    Jose P. Pinto, R. Kalathur, R. Machado , J. Xavier, J. Bragança, and M.E Futschik (2014) StemCellNet: an interactive platform for network-oriented investigations in stem cell biology, Heart without Boarders, International Conference, Porto, Portugal (abstract)


Software developed