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Pietro Liò

Publications and source records attributed to Pietro Liò.

12 recordsLinked to original sources
PubMed2006

Computational framework for the prediction of transcription factor binding sites by multiple data integration.

Control of gene expression is essential to the establishment and maintenance of all cell types, and its dysregulation is involved in pathogenesis of several diseases. Accurate computational predictions of transcription factor regulation may thus help in understanding complex diseases, including mental disorders in which dysregulation of neural gene expression is thought to play a key role. However, biological mechanisms underlying the regulation of gene expression are not completely understood, and predictions via bioinformatics tools are typically poorly specific. We developed a bioinformatics workflow for the prediction of transcription factor binding sites from several independent datasets. We show the advantages of integrating information based on evolutionary conservation and gene expression, when tackling the problem of binding site prediction. Consistent results were obtained on a large simulated dataset consisting of 13050 in silico promoter sequences, on a set of 161 human gene promoters for which binding sites are known, and on a smaller set of promoters of Myc target genes. Our computational framework for binding site prediction can integrate multiple sources of data, and its performance was tested on different datasets. Our results show that integrating information from multiple data sources, such as genomic sequence of genes' promoters, conservation over multiple species, and gene expression data, indeed improves the accuracy of computational predictions.

Animals↗
PubMed2005

A novel algorithm and web-based tool for comparing two alternative phylogenetic trees.

SUMMARY: We describe an algorithm and software tool for comparing alternative phylogenetic trees. The main application of the software is to compare phylogenies obtained using different phylogenetic methods for some fixed set of species or obtained using different gene sequences from those species. The algorithm pairs up each branch in one phylogeny with a matching branch in the second phylogeny and finds the optimum 1-to-1 map between branches in the two trees in terms of a topological score. The software enables the user to explore the corresponding mapping between the phylogenies interactively, and clearly highlights those parts of the trees that differ, both in terms of topology and branch length. AVAILABILITY: The software is implemented as a Java applet at http://www.mrc-bsu.cam.ac.uk/personal/thomas/phylo_comparison/comparison_page.html. It is also available on request from the authors.

Algorithms↗
PubMed2005

The origin and evolution of operons: the piecewise building of the proteobacterial histidine operon.

The structure and organization of 470 histidine biosynthetic genes from 47 different proteobacteria were combined with phylogenetic inference to investigate the mechanisms responsible for assembly of the his pathway and the origin of his operons. Data obtained in this work showed that a wide variety of different organization strategies of his gene arrays exist and that some his genes or entire his operons are likely to have been horizontally transferred between bacteria of the same or different proteobacterial branches. We propose a "piecewise" model for the origin and evolution of proteobacterial his operons, according to which the initially scattered his genes of the ancestor of proteobacteria coded for monofunctional enzymes (except possibly for hisD) and underwent a stepwise compacting process that reached its culmination in some gamma-proteobacteria. The initial step of operon buildup was the formation of the his "core," a cluster consisting of four genes (hisBHAF) whose products interconnect histidine biosynthesis to both de novo synthesis of purine metabolism and that occurred in the common ancestor of the alpha/beta/gamma branches, possibly after its separation from the epsilon one. The following step was the formation of three mini-operons (hisGDC, hisBHAF, hisIE) transcribed from independent promoters, that very likely occurred in the ancestor of the beta/gamma-branch, after its separation from the alpha one. Then the three mini-operons joined together to give a compact operon. In most gamma-proteobacteria the two fusions involving the gene pairs hisN-B and hisI-E occurred. Finally the gamma-proteobacterial his operon was horizontally transferred to other proteobacteria, such as Campylobacter jejuni. The biological significance of clustering of his genes is also discussed.

Databases, Nucleic Acid↗
PubMed2004

Phylogenetic and structural analysis of mitochondrial complex I proteins.

Our understanding of the evolutionary process would benefit from a better understanding of protein structural changes during evolution. I report that combining phylogenetic and structural analyses of the mitochondrial protein sequences allow to identify important differences between protostomes and deuterostomes mitochondrial proteins: (1) ND5, and with less intensity, ND1, ND2 and ND4, have significantly lower hydrophobicity in deuterostomes than in proterostomes; (2) the C-terminal half portion of ND5 has lower hydrophobicity than the N-terminal half portion, suggesting the presence of larger extra-membrane hydrophilic loops in deuterostomes with respect to protostomes; (3) substitution matrices generated from different complex I proteins show different patterns of amino acid substitutions, suggesting that mitochondrial proteins have different evolutionary dynamics. I hypothesise that the better performances in phylogenetic inference of ND5 with respect to other mitochondrial proteins may be related to its position inside the complex I.

Amino Acid Substitution↗
PubMed2004

Identification of DNA regulatory motifs using Bayesian variable selection.

MOTIVATION: Understanding the mechanisms that determine gene expression regulation is an important and challenging problem. A common approach consists of identifying DNA-binding sites from a collection of co-regulated genes and their nearby non-coding DNA sequences. Here, we consider a regression model that linearly relates gene expression levels to a sequence matching score of nucleotide patterns. We use Bayesian models and stochastic search techniques to select transcription factor binding site candidates, as an alternative to stepwise regression procedures used by other investigators. RESULTS: We demonstrate through simulated data the improved performance of the Bayesian variable selection method compared to the stepwise procedure. We then analyze and discuss the results from experiments involving well-studied pathways of Saccharomyces cerevisiae and Schizosaccharomyces pombe. We identify regulatory motifs known to be related to the experimental conditions considered. Some of our selected motifs are also in agreement with recent findings by other researchers. In addition, our results include novel motifs that constitute promising sets for further assessment. AVAILABILITY: The Matlab code for implementing the Bayesian variable selection method may be obtained from the corresponding author.

Algorithms↗
PubMed2003

Investigating the evolution and structure of chemokine receptors.

Chemokine receptors represent a prime target for the development of novel therapeutic strategies in a variety of disease processes, including inflammation, allergy and neoplasia. Here we use maximum likelihood methods and bootstrap methods to investigate both the phylogenetic relationships in a large set of human chemokine receptor sequences and the relationships between chemokine receptors and their nearest neighbors. We found that CCR and CXCR families are not homogeneous. We also provide evidences that angiotensin receptors are the closest neighbors. Other close neighbors include opioid, somatostatin and melanin-concentrating hormone receptors. The phylogenetic analysis suggests ancient paralogous relationships and establishes a link between immune, metabolic and neural systems modulation. We complement our findings with a structural analysis based on wavelet methods of the major branches of chemokine receptors phylogeny. We hypothesize that receptors very close in the tree can form heterodimers. Our analyses reveal different characteristics of amino acid hydrophobicity and volume propensity in the different subfamilies. We also found that the second extra-cytoplasmic loop has higher rates of evolution than the internal loops and transmembrane segments, suggesting that selection, shifting, reassignments and broadening of receptor binding specificities involve mainly this loop.

Evolution, Molecular↗
PubMed2003

Statistical bioinformatic methods in microbial genome analysis.

It is probable that, increasingly, genome investigations are going to be based on statistical formalization. This review summarizes the state of art and potentiality of using statistics in microbial genome analysis. First, I focus on recent advances in functional genomics, such as finding genes and operons, identifying gene conversion events, detecting DNA replication origins and analysing regulatory sites. Then I describe how to use phylogenetic methods in genome analysis and methods for genome-wide scanning for positively selected amino acids. I conclude with speculations on the future course of genome statistical modeling.

Computational Biology↗
PubMed2003

Dimensionality and dependence problems in statistical genomics.

Genome studies have become central to a wide range of biological areas. This paper is intended to discuss the state of art and potentiality of using statistics in genome comparison. The problem of dependence and dimensionality in genome data is addressed first. The focus is on using phylogenetic methods in genome comparison, on combining sequence and gene expression data to find transcription sites, and on multiple hypothesis testing in gene expression data. The paper concludes with speculations on the future course of statistical and bioinformatics analyses.

Animals↗
PubMed2003

Wavelets in bioinformatics and computational biology: state of art and perspectives.

MOTIVATION: At a recent meeting, the wavelet transform was depicted as a small child kicking back at its father, the Fourier transform. Wavelets are more efficient and faster than Fourier methods in capturing the essence of data. Nowadays there is a growing interest in using wavelets in the analysis of biological sequences and molecular biology-related signals. RESULTS: This review is intended to summarize the potential of state of the art wavelets, and in particular wavelet statistical methodology, in different areas of molecular biology: genome sequence, protein structure and microarray data analysis. I conclude by discussing the use of wavelets in modeling biological structures.

Algorithms↗
PubMed2002

Modeling mitochondrial protein evolution using structural information.

We present two new models of protein sequence evolution based on structural properties of mitochondrial proteins. We compare these models with others currently used in phylogenetic analyses, investigating their performance over both short and long evolutionary distances. We find that our models that incorporate secondary structure information from mitochondrial proteins are statistically comparable with existing models when studying 13 mitochondrial protein data sets from eutherian mammals. However, our models give a significantly improved description of the evolutionary process when used with 12 mitochondrial proteins from a broader range of organisms including fungi, plants, protists, and bacteria. Our models may thus be of use in estimating mitochondrial protein phylogenies and for the study of processes of mitochondrial protein evolution, in particular for distantly related organisms.

Evolution, Molecular↗
PubMed2002

Investigating the relationship between genome structure, composition, and ecology in prokaryotes.

Our thesis is that the DNA composition and structure of genomes are selected in part by mutation bias (GC pressure) and in part by ecology. To illustrate this point, we compare and contrast the oligonucleotide composition and the mosaic structure in 36 complete genomes and in 27 long genomic sequences from archaea and eubacteria. We report the following findings (1) High-GC-content genomes show a large underrepresentation of short distances between G(n) and C(n) homopolymers with respect to distances between A(n) and T(n) homopolymers; we discuss selection versus mutation bias hypotheses. (2) The oligonucleotide compositions of the genomes of Neisseria (meningitidis and gonorrhoea), Helicobacter pylori and Rhodobacter capsulatus are more biased than the other sequenced genomes. (3) The genomes of free-living species or nonchronic pathogens show more mosaic-like structure than genomes of chronic pathogens or intracellular symbionts. (4) Genome mosaicity of intracellular parasites has a maximum corresponding to the average gene length; in the genomes of free-living and nonchronic pathogens the maximum occurs at larger length scales. This suggests that free-living species can incorporate large pieces of DNA from the environment, whereas for intracellular parasites there are recombination events between homologous genes. We discuss the consequences in terms of evolution of genome size. (5) Intracellular symbionts and obligate pathogens show small, but not zero, amount of chromosome mosaicity, suggesting that recombination events occur in these species.

AT Rich Sequence↗