Gianluca Della Vedova

Analysis of Bacterial Community Composition by Oligonucleotide Fingerprinting of rRNA Genes

ABSTRACT One of the first steps in characterizing an ecosystem is to describe the organisms inhabiting it. For microbial studies, experimental limitations have hindered the ability to depict diverse communities. Here we describe oligonucleotide fingerprinting of rRNA genes (OFRG), a method that permits identification of arrayed rRNA genes (rDNA) through a series of hybridization experiments using small DNA probes. To demonstrate this strategy, we examined the bacteria inhabiting two different soils. Analysis of 1,536 rDNA clones revealed 766 clusters grouped into five major taxa: Bacillus, Actinobacteria, Proteobacteria, and two undefined assemblages. Soil-specific taxa were identified and then independently confirmed through cluster-specific PCR of the original soil DNA. Near-species-level resolution was obtained by this analysis as clones with average sequence identities of 97% were grouped in the same cluster. A comparison of these OFRG results with the results obtained in a denaturing gradient gel electrophoresis analysis of the same two soils demonstrated the significance of this methodological advance. OFRG provides a cost-effective means to extensively analyze microbial communities and should have applications in medicine, biotechnology, and ecosystem studies.

The Haplotyping problem: an overview of computational models and solutions

The investigation of genetic differences among humans has given evidence that mutations in DNA sequences are responsible for some genetic diseases. The most common mutation is the one that involves only a single nucleotide of the DNA sequence, which is called a single nucleotide polymorphism (SNP). As a consequence, computing a complete map of all SNPs occurring in the human populations is one of the primary goals of recent studies in human genomics. The construction of such a map requires to determine the DNA sequences that from all chromosomes. In diploid organisms like humans, each chromosome consists of two sequences calledhaplotypes. Distinguishing the information contained in both haplotypes when analyzing chromosome sequences poses several new computational issues which collectively form a new emerging topic of Computational Biology known asHaplotyping.This paper is a comprehensive study of some new combinatorial approaches proposed in this research area and it mainly focuses on the formulations and algorithmic solutions of some basic biological problems. Three statistical approaches are briefly discussed at the end of the paper.

The complexity of multiple sequence alignment with SP-score that is a metric

This paper analyzes the computational complexity of computing the optimal alignment of a set of sequences under the sum of all pairs (SP) score scheme. We solve an open question by showing that the problem is NP-complete in the very restricted case in which the sequences are over a binary alphabet and the score is a metric. This result establishes the intractability of multiple sequence alignment under a score function of mathematical interest, which has indeed received much attention in biological sequence comparison.

Oligonucleotide Fingerprinting of rRNA Genes for Analysis of Fungal Community Composition

ABSTRACT Thorough assessments of fungal diversity are currently hindered by technological limitations. Here we describe a new method for identifying fungi, oligonucleotide fingerprinting of rRNA genes (OFRG). ORFG sorts arrayed rRNA gene (ribosomal DNA [rDNA]) clones into taxonomic clusters through a series of hybridization experiments, each using a single oligonucleotide probe. A simulated annealing algorithm was used to design an OFRG probe set for fungal rDNA. Analysis of 1,536 fungal rDNA clones derived from soil generated 455 clusters. A pairwise sequence analysis showed that clones with average sequence identities of 99.2% were grouped into the same cluster. To examine the accuracy of the taxonomic identities produced by this OFRG experiment, we determined the nucleotide sequences for 117 clones distributed throughout the tree. For all but two of these clones, the taxonomic identities generated by this OFRG experiment were consistent with those generated by a nucleotide sequence analysis. Eighty-eight percent of the clones were affiliated with Ascomycota, while 12% belonged to Basidiomycota. A large fraction of the clones were affiliated with the genera Fusarium (404 clones) and Raciborskiomyces (176 clones). Smaller assemblages of clones had high sequence identities to the Alternaria, Ascobolus, Chaetomium, Cryptococcus, and Rhizoctonia clades.

Reconciling a gene tree to a species tree under the duplication cost model

The general problem of reconciling the information from evolutionary trees representing the relationships between distinct gene families is of great importance in bioinformatics and has been popularized among the computer science researchers by Ma et al. [From gene trees to species trees, SIAM J. Comput. 30(3) (2000) 729-752] where the authors pose the intriguing question if a certain definition of minimum tree that reconciles a gene tree and a species tree is correct. We answer affirmatively to this question; moreover, we show an efficient algorithm for computing such minimum-leaf reconciliation trees and prove the uniqueness of such trees. We then tackle some different versions of the biological problem by showing that the exemplar problem, arising from the exemplar analysis of multigene genomes, is NP-hard even when the number of copies of a given label is at most two. Finally, we introduce two novel formulations for the problem of recombining evolutionary trees, extending the gene duplication problem studied in [Ma et al., From gene trees to species trees, SIAM J. Comput. 30(3) (2000) 729-752; M. Fellows et al., On the multiple gene duplication problem, in: Proc. Ninth Internat. Symp. on Algorithms and Computation (ISAAC98), 1998; R. Page, Maps between trees and cladistic analysis of historical associations among genes, Systematic Biology 43 (1994) 58-77; R.M. Page, J. Cotton, Vertebrate phylogenomics: reconciled trees and gene duplications, in: Proc. Pacific Symp. on Biocomputing 2002 (PSB2002), 2002, pp. 536-547; R. Guigo et al., Reconstruction of ancient molecular phylogeny, Mol. Phy. and Evol. 6(2) (1996) 189-213], and we give an exact algorithm (via dynamic programming) for one of these formulations.

Tools and data services registry: a community effort to document bioinformatics resources

Life sciences are yielding huge data sets that underpin scientific discoveries fundamental to improvement in human health, agriculture and the environment. In support of these discoveries, a plethora of databases and tools are deployed, in technically complex and diverse implementations, across a spectrum of scientific disciplines. The corpus of documentation of these resources is fragmented across the Web, with much redundancy, and has lacked a common standard of information. The outcome is that scientists must often struggle to find, understand, compare and use the best resources for the task at hand. Here we present a community-driven curation effort, supported by ELIXIR—the European infrastructure for biological information—that aspires to a comprehensive and consistent registry of information about bioinformatics resources. The sustainable upkeep of this Tools and Data Services Registry is assured by a curation effort driven by and tailored to local needs, and shared amongst a network of engaged partners. As of November 2015, the registry includes 1785 resources, with depositions from 126 individual registrations including 52 institutional providers and 74 individuals. With community support, the registry can become a standard for dissemination of information about bioinformatics resources: we welcome everyone to join us in this common endeavour. The registry is freely available at https://bio.tools.

Parameterized complexity of k-anonymity: hardness and tractability

The problem of publishing personal data without giving up privacy is becoming increasingly important. A precise formalization that has been recently proposed is the k-anonymity, where the rows of a table are partitioned into clusters of sizes at least k and all rows in a cluster become the same tuple after the suppression of some entries. The natural optimization problem, where the goal is to minimize the number of suppressed entries, is hard even when the stored values are over a binary alphabet or the table consists of a bounded number of columns. In this paper we study how the complexity of the problem is influenced by different parameters. First we show that the problem is W[1]-hard when parameterized by the value of the solution (and k). Then we exhibit a fixed-parameter algorithm when the problem is parameterized by the number of columns and the number of different values in any column. Finally, we prove that k-anonymity is still APX-hard even when restricting to instances with 3 columns and k=3.

Exemplar Longest Common Subsequence

In this paper, we investigate the computational and approximation complexity of the Exemplar Longest Common Subsequence (ELCS) of a set of sequences (ELCS problem), a generalization of the Longest Common Subsequence problem, where the input sequences are over the union of two disjoint sets of symbols, a set of mandatory symbols and a set of optional symbols. We show that different versions of the problem are APX-hard even for instances with two sequences. Moreover, we show that the related problem of determining the existence of a feasible solution of the ELCS of two sequences is NP-hard. On the positive side, we first present an efficient algorithm for the ELCS problem over instances of two sequences where each mandatory symbol can appear in total at most three times in the sequences. Furthermore, we present two fixed-parameter algorithms for the ELCS problem over instances of two sequences where the parameter is the number of mandatory symbols.

Experimenting an approximation algorithm for the LCS

The problem of finding the longest common subsequence (lcs) of a given set of sequences over an alphabet Σ occurs in many interesting contexts, such as data compression and molecular biology, in order to measure the “similarity degree” among biological sequences. Since the problem is NP-complete in its decision version (i.e. does there exist a lcs of length at least k, for a given k?) even over fixed alphabet, polynomial algorithms which give approximate solutions have been proposed. Among them, Long Run (LR) is the only one with guaranteed constant performance ratio. In this paper, we give a new approximation algorithm for the longest common subsequence problem: the Expansion Algorithm (EA). First of all, we prove that the solution found by the Expansion Algorithm is always at least as good as the one found by LR. Then we report the results of an experimentation with two different groups of instances, which show that EA clearly outperforms Long Run in practice.

On the Approximation of Correlation Clustering and Consensus Clustering

The Correlation Clustering problem has been introduced recently [N. Bansal, A. Blum, S. Chawla, Correlation Clustering, in: Proc. 43rd Symp. Foundations of Computer Science, FOCS, 2002, pp. 238-247] as a model for clustering data when a binary relationship between data points is known. More precisely, for each pair of points we have two scores measuring the similarity and dissimilarity respectively, of the two points, and we would like to compute an optimal partition where the value of a partition is obtained by summing up the similarity scores of pairs involving points from the same cluster and the dissimilarity scores of pairs involving points from different clusters. A closely related problem is Consensus Clustering, where we are given a set of partitions and we would like to obtain a partition that best summarizes the input partitions. The latter problem is a restricted case of Correlation Clustering. In this paper we prove that Minimum Consensus Clustering is APX-hard even for three input partitions, answering an open question in the literature, while Maximum Consensus Clustering admits a PTAS. We exhibit a combinatorial and practical 45-approximation algorithm based on a greedy technique for Maximum Consensus Clustering on three partitions. Moreover, we prove that a PTAS exists for Maximum Correlation Clustering when the maximum ratio between two scores is at most a constant.