4. Modeling Splicing from Chromatin The search of sequence prerequisites for nucleosome positioning has been a long-standing problem at the intersection of chromatin structure and gene regulation. With the use of structural information directly related to the primary DNA sequence we propose a new property of natural nucleosome forming sequences, which is inherently related to their intrinsic curvature and its symmetry. A measure of this property has been introduced and a corresponding method validated against novel high quality datasets of human nucleosomes, obtained through close collaboration with CRG’s Chromatin and Gene Expression Group (Miguel Beato). We are also continuing our close collaboration with the group of Juan Valcárcel, from the CRG’s Gene Regulation programs focusing on the investigation of the mechanisms through which splice signals are recognized and processed. We are developing new methods to infer sequences that may play a role in the regulation of alternative splicing, and have continued investigating the dynamics of the evolution of U12 introns.
5. Development of Methods for Evolutionary Genomics Studies In 2011 we published an article (Kedzierska et al., 2011) that describes the development of a novel method for phylogenetic reconstruction (SPIn). This method is based on linear INvariants (SPIn), which uses recent insights on linear invariants to characterize a model of nucleotide evolution for phylogenetic mixtures on any number of components. SPIn is unique in which it does not require an input tree and is designed to deal with non-homogeneous phylogenetic data consisting of multiple sequence alignments showing different patterns of evolution, i.e. concatenated genes, exons and/or introns. We also concluded a collaborative effort focusing on the CTCF vertebrate insulator protein. We have found that constitutive sites form mandatory boundaries within vertebrate genomes are preferably located close to transcription factor-encoding genes involved in development (Martin et al., 2011).
PUBLICATIONS Gonzalez-Porta, M, Calvo M, Sammeth M, Guigo R. “Estimation of alternative splicing variability in human populations”. Genome Research, 22(3):528-3 (2011). Kedzierska AM, Drton M, Guigó R and Casanellas M. “SPIn: model selection for phylogenetic mixtures via linear invariants”. Mol Biol Evol, 29(3):929-37 (2011). Martin et al. (incl. R. Guigo). “Genome-wide CTCF distribution in vertebrates defines equivalent sites that aid the identification of disease-associated genes”. Nat Struct Mol Biol, 18(6):708-14. Erratum in: Nat Struct Mol Biol, 2011, 18(9):1084 (2011). Derrien T, Guigó R. [Long non-coding RNAs with enhancer-like function in human cells]. Med Sci (Paris), 27(4):359-61 (2011). Maxwell et al. (incl. J. Curado, H. Tilgner and R. Guigo). “Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer”. PLoS Biol, 9(11):e1001199 (2011). Mudge et al. (incl. T. Alioto, T. Derrien and R. Guigo) “The origins, evolution and functional potential of alternative splicing in vertebrates”. Mol Biol Evol, 28(10):2949-59 (2011).
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Annual Report 2011 .97