New Sequencing Technologies: Applications and Impact

1

Deep sequencing of Trypanosoma cruzi life cycle transcriptome

Daniela Parada Pavoni, Christian Macagnan Probst, Rita de Cássia Pontello Rampazzo, Marco Aurélio Krieger.

Trypanosoma cruzi life cycle transcriptome was analyzed by deep sequencing with ABI SOLiD equipment. A total of ~450 million reads from 25 samples comprising the four major stages of T. cruzi wee obtained. This dataset allowed us to identify differentially expressed genes, as well as modules of co-expression.

2

A bin-based enrichment level threshold (BELT) algorithm to analyze ChIP-seq data

Xun Lan, Sankaran Kasiviswanathan, Jeff Apostolos, Brian A. Kennedy, Tim H.-M. Huang and Victor X. Jin

With the availability of large biological datasets derived from recent ChIP-seq technology, biologists using such technologies face major challenges. We present a novel algorithm,BELT, to analyze ChIP-seq data. The real value of our algorithm was assessed by synthetic data and four well-characterized human transcription factors' ChIP-seq data.

3

16S rRNA hypervariable tag pyrosequencing for the study of microbial diversity in a protected coastal lagoon (Laguna de Rocha, Uruguay)

Cecilia Alonso, Claudia Piccini

Massively parallel pyrosequencing of hypervariable regions from 16S rRNA was used to address bacterioplankton diversity in a coastal lagoon of Uruguay. This tool allowed the identification of a significantly higher number of bacterial groups than 16S rRNA clone libraries and provided valuable information about rare bacterial species.

4

Simulation of Digital Northerns and RNA-Seq Samba

Michael Sammeth, Paolo Ribeca, Roderic Guigó

Several procedures have been proposed to apply high-throughput sequencing to cDNA libraries constructed from entire cellular RNA complements, so-called "RNA-Seq". We developed models to mimic these experimental pipelines and study sources and impact of biases introduced in the process. Subsequently conducted simulations pinpoint bioinformatics vulnerabilities of RNA-Seq data analyzes.

5

mRNA decay profiles in Trypanosoma cruzi obtained by deep sequencing

Eduardo Lemons Francisco, Daniela Parada Pavoni, Rita de Cássia Pontello Rampazzo, Marco Aurélio Krieger, Christian Macagnan Probst

Trypanosoma cruzi regulates gene expression post-transcriptionally, and little is known about regulatory networks. mRNA decay profiles represent the final result of an intrincated series of control steps. Next-gen sequencing enables quantitative assessment of mRNA decay, which can be integrated with other datasets for data mining regarding gene expression network identification.

6

A centralized and scalable infrastructure approach to support next-generation sequencing at the National Institute of Allergy and Infectious Diseases

Nick Weber, Vivek Gopalan, Mariam Quiñones, Hugo Hernandez, Robert Reed, Kim Kassing, Yentram Huyen, Michael Tartakovsky

Managing the storage, transfer, processing and analysis of terabytes of NGS data can be overwhelming for researchers. NIAID's approach to address these challanges by developing a centralized and scalable infrastructure highlights the need for a cooperative partnership between bench researchers, computational scientists, and IT professionals in order to advance modern scientific exploration and discovery.

Protein Structure and Function

7

A Study of Hydrophobic Effect on the Protein Folding Using Monte Carlo in 2D Lattice and Cubic lattice

Luis Scott, Pierre Tisseur, Adriano Faria

Several works on hydrophobicity has been done in an attempt to answer the following question: do compact rnconformations due to hydrophobic collapse help protein folding? In this work, the HP model, a Cubic lattice and Monte Carlo Method are used to study the effect hydrophobic on the folding problem.

8

Using genetic algorithms and rotamer library to investigate protein-ligand docking

Luis Scott, Angelica Lima, Eric Phillot

The docking problem is posed as an optimization problem, where the objective is to minimize the intermolecular interaction energy between the molecules. Here, we are developing an applications of methods that combine techniques like Genetic Algorithms and Rotamer Library and studied the docking of HIV-1 Protease with different ligands.

9

Applying data mining to investigate the protein folding and extract rules of formation of secondary structure

Luis Scott, Maria Barioni, Digo Estelle

This work aims discusses the possibilities to use distinct techniques of data mining to investigate and to extract the rules for the formation of secondary structure of proteins. In this work we investigated the use a special data bank and a association rules to predict protein structure.

10

Modelling and Evaluation of the Tridimensional Structure of E5, an Oncoprotein from the Human Papillomavirus (HPV) Types 06 and 16

Nilson Nicolau Junior, Silvana Giuliatti

Invasive cervical carcinoma arises in persistent infection by human papillomavirus (HPV). Due the importance of the oncoprotein E5 in the carcinogenesis, obtaining a 3D structure model of it may facilitate studies involving inhibitor-protein docking experiments. This present work model and validate E5 protein structures from HPV type 06 and 16.

11

In silico screening for Phospholipase A2 of Apis Mellifera with Fragment Library

Daniel M. M. Jorge, Vinicius B. da Silva, Carlos H. T. P. Silva, Andreimar M. Soares, Silvana Giuliatti

Phospholipases A2 (PLA2s) are enzymes that catalyze the hydrolysis of the sn-2 acyl bond of glycerophospholipids. The aim of this project was predict potential inhibitors against bvPLA2. The best score compost has been named Molecule 593. Fifty proposals were selected and also should be evaluated against bvPLA2.

12

Homology relationship based on the amino acid properties

Verónica Alvarez and Luis Diambra

We present a complementary manner to determine homologies between proteins. This alternative is based on the properties of the amino acid sequences and could be useful to detect distant homology relationship.

13

Structural comparison and classification of the catalytic domains in DNA polymerases

Alex W. Slater and Francisco Melo

We have performed the structural comparison of all catalytic domains in DNA polymerases whose 3D structure is currently known. A new classification have been obtained, that provides hints for distant relationship between families that can not be explored by sequence-based methods alone.

14

New insights in oligopeptidases inhibition: molecular dynamics studies of substrate/inhibitor accommodation

Jorge H. Fernandez

Oligopeptidases are important enzymes critical role in cardiovascular, renal and other disease and an attractive target for drug design. In our work X-ray data was combined with modeling, docking and molecular dynamics to study the evolutive conservation of residues that allow the enzyme-substrate/inhibitors contacts. Applications in drug desing are discussed.

15

A simple solution to undercome pitfalls of structural alignment methods in the classification of protein structures where high sequence divergence exists

Javier Castellanos, Alex W. Slater and Francisco Melo F.

Structural alignment is a necessary step when classifying proteins according to its fold. In this work we evaluate the performance of five structural alignment software using structures from the DNA polymerize family. Our results suggest that none of the software is able to provide the best solution consistently.

16

PDIdb: a novel database containing the three-dimensional interfaces of protein-DNA complexes

Tomas Norambuena and Francisco Melo

PDIdb is a repository containing relevant structural information of Protein-DNA complexes. It is focused on each specific atomic interface rather than on the separated binding partners. This database will be useful for prediction of protein binding sites in DNA, engineering and design of new transcription factors, and also will serve educational and teaching purposes.

17

Classification of enzyme function according to similarities in reaction mechanisms and common substrate substructures

Daniel E. Almonacid, Patricia C. Babbitt

We classified functionally analogous enzymes from the MACiE database and homologous superfamilies of enzymes from the Structure Function Linkage Database based on similarity of reaction mechanisms and common substrate substructures. We conclude that these new functional classifications are orthogonal and thus complementary to current classifications based on sequence and structure.

18

Reconstruction of MHC alleles by cross modeling and structural assessment

Cassiana Fülber, Samuel Cibulski, Dinler Antunes, Maurício Rigo, José Chies, Marialva Sinigaglia, Gustavo Vieira

The Major Histocompatibility Complex presents endogenous peptides on cell's surface for recognition by the immune system. It is essential to know its structure to understand how it interacts with antigens. We performed a cross modeling to verify if it is possible to model MHC alleles with the correct structural requirements.

19

A new approach to fast calculation of Atomic Contact Energy for protein-protein interaction prediction

Cristian Sebastian Rocha, Luis Gómez Déniz

In this paper, we propouse a new method to calculate the ACE potential through FFT correlation to reduce the computational complexity. We had compared our results, about solvatation grid and docking prediction, with the original ACE potential.

20

A simplified 1-D representation of electrostatic surface properties of modeled protein structures enables screening for evolutionary adaptive protein sites

Dietlind L. Gerloff, Shakir Ali, Marcos Woehrmann

We have developed a novel simplified representation of the electrostatic molecular surfaces of proteins: 1-D "electrostatic surface profiles". I will discuss how predictions of interaction sites under adaptive evolution pressure were made from comparisons of the 1-D surface profiles of the 30 homologous domains in Complement Receptor 1 (CR1).

21

Distribution and extension of protein conformational diversity

Ezequiel Iván Juritz, Nicolás Palopoli, Sebastián Fernández Alberti, Gustavo Parisi

Knowledge of protein conformational diversity is a key feature for comprehension and adjustment of its biological functions. Here we present a protein conformational diversity database, complemented with structural, functional and physico-chemical data from other databases to study the origin and extension of the conformational diversity.

22

Quality assessment of protein structure models using evolutionary information

Nicolas Palopoli, Ezequiel Juritz, Sebastián Fernandez Alberti, Diego Gomez Casati, Gustavo Parisi

We present the results of using evolutionary information for the assessment of protein structure models in CASP8 through our new method BEEP. This method provides a novel approach for model evaluation by identifying a set of native-like models which best represent the amino acid substitution pattern in homologous proteins.

23

Structural and Biological Analysis of Retromer Complex in the protozoan parasite Giardia lamblia

Silvana L Miras, María R Rivero, Andrea S Ropolo and María C Touz.

Giardia lamblia is an early branching microorganism that passes through two stages in their biological life cycle: the trophozoite and the cyst. Although without a typical Golgi apparatus there is a specific protein trafficking. In this work, we seek to analyze whether a retromer complex, that mediates the retrograde transport of transmembrane proteins exists.

24

Role of heme distortion on oxygen affinity in heme proteins: the protoglobin case

Damián E. Bikiel, Flavio Forti, Leonardo Boechi, Marco Nardini, F. Javier Luque, Marcelo A. Martí, and Darío A. Estrin

The porphyrin ring of some hemeproteins exhibits significant distortions from its ideal planar structure, but the impact of these distortions on the chemical properties of the heme is yet uncertain. A systematic study focused on the effects of the distortion of the macrocycle on the affinity for O2 is presented.

25

A new method combining mutual information and conservation improves the detection of catalytic sites in proteins

Elin Teppa, Tomas Di Doménico, Morten Nielsen and Cristina Marino Buslje

Mutual-information theory predicts positional correlations in a multiple-sequence alignment. On the other hand, Conservation often reveals catalytic residues. However, non-catalytic residues may be conserved. We propose a method that improves the detection of catalytic residues by combining a MI-network score with a conservation score for each position in the alignment.

26

Comparison of structural, dynamical and protein carbohydrate interaction properties of human galectins

Carlos M. A. Guardia, Diego F. Gauto, Santiago Di Lella, Gabriel A. Rabinovich, Marcelo A. Martí and Darío A. Estrin

Galectins constitute a familiy of multi-functional lectin proteins extensively distributed in a variety of tissues. In this work, we studied by means of molecular dynamics simulations structural, dynamic and functional properties of all members of this family in order to understand the molecular basis of their distinct functions.

Sequence Analysis, Comparative Genomics and Evolution

27

In silico testing of 23S rRNA primers for further use in cyanobacterial mats biodiversity studies

Cristian Coman, Adriana Bica, Bogdan Druga, Ana Nicoara and Nicolae Dragos

This study presents the importance of computational biology in microbial biodiversity studies in the crucial step of primer design and in silico testing. After the primers were constructed, they were tested on more than 2500 bacterial 23S rRNA sequences (ARB-SILVA) to test their specificity and their possible application in phylogenetic studies.

28

Protein Data Integration for Phylogenetic Data Mining

Humberto Razente, Antonio Braz, Luis Scott

In order to investigate a hypothesis, a researcher must deal with thousands of sequences. The work includes the classification, selection, and linkage of sequence names from different sources. Data integration is fundamental to phylogenetic studies, allowing structures, transcription and translation levels to be used for a single objective.

29

Genomic Ecology: genes competing for a metabolic niche?

Marcos Catanho, Ana Carolina Ramos Guimarães, Thomas Dan Otto, Fernando Alvarez-Valin, Wim Degrave & Antonio Basílio de Miranda

Previous works performed by other groups suggest that the fraction of enzymatic activities in which multiple events of independent origin have occurred may be substantial. Here, we investigate the variability/evolution of metabolic pathways in prokaryotes, analyzing the frequency, distribution and extinction patterns of putative analogous enzymes in the glycolysis/gluconeogenesis pathway.

30

A computational pipeline for diagnostic biomarker discovery in the human pathogen Trypanosoma cruzi

Santiago Carmona, Paula Sartor, Susana Leguizamón, Oscar Campetella and Fernán Agüero

A bioinformatic strategy was developed to identify peptidic antigens in the genome of Trypanosoma cruzi. A 12-residue sliding window assigned scores to each peptide based on a number of properties. The highest scoring peptides were synthesized and tested as candidate serodiagnostic biomarkers for Chagas disease.

31

Compositional Profile of the Human Genome at the Chromosome Level

Victor Sabbia, Hector Romero, Hector Musto, Hugo Naya

We studied the compositional differences among chromosomes, considering structural and functional aspects using the chromosomes as the units of analysis.The results support the existence of a link between composition and spatial/structural/functional features of entire chromosomes.

32

Analogous enzymes inside the Tritryps genomes

Ana Carolina Ramos Guimarães, Wim Maurits Degrave, Antonio Basílio de Miranda

The existence of alternative forms to perform the same enzymatic function as a result of multiple events of independent origin had been previously described and called as analogous enzymes. However, the possibility of occurrence of functional analogues inside the genome of single organism had not been observed.

33

Comparative microbial genomics in Pasteurellaceae family using second generation sequencing

Isabelle da Piedade, Timothy J Johnson, Anders M Bojesen

Pasteurellaceae is an increasing and diverse family of Gram-negative bacteria that include primary pathogens, such as Haemophilus influenza, Pasteurella multocida and Actinobacillus pleuropneumoniae, as well as several potential pathogens. In this study, we present an extensive comparative analysis of different clades of the Pasteurellaceae family using second generation sequencing.

34

The Genome Comparison Project and the Protein World Database

Thomas Dan Otto, Marcos Catanho, Cristian Tristão, Márcia Bezerra, Renan Mathias Fernandes, Guilherme Steinberger Elias, Alexandre Capeletto Scaglia, Bill Bovermann, Viktors Berstis, Sergio Lifschitz, Antonio Basílio de Miranda & Wim Degrave

Many analyses in modern research are based on biological sequence comparisons, resulting in functional, evolutionary, and structural inferences. ProteinWorldDB represents a major effort to create a reliable and consistent dataset of cross-comparisons of the whole protein content encoded in hundreds of completely sequenced genomes using a rigorous dynamic programming approach.

35

Searching for signals in the Tritryps genomes

Pablo Smircich, Gustavo Cerqueira, Najib El-Sayed, Beatriz Garat

The Tritryps present unique biological features. Particularly, the search for transcription initiation sites has been elusive so far. We aim to determine structural characteristics of already described sites to establish a prediction system for putative binding sites. We have recognized conserved features in ARNPI promoters that may serve this purpose.

36

Comparative proteome analysis of protozoan parasites: tandem repeat proteins and epitope predictions

Tiago Mendes, Frascisco Lobo, Leandro Freitas, Tiago Rodrigues, Daniella Bartholomeu

We have performed in silico analysis searching for perfect and degenerated repeats in the predicted proteome of nine parasites. The repetitive content of B cell and T cell predicted epitopes and the subcellular location of the corresponding proteins were also analyzed. The results show differences between extracellular and intracellular parasites.

37

Codon usage analysis in Enterobacteriaceae: towards the detection of ancestral optimal triplets

Juan Baraibar, Andrés Iriarte, Héctor Romero, Héctor Musto

We tracked the influence of natural selection in the history of Enterobacteriaceae and map the dynamic of optimal codons in the lineage. We propose: 1) natural selection is one of the main evolutive forces affecting synonymous codon usage; 2) 16 codons may have been optimal in the common ancestor.

38

Selection to less thymine dimmers content in the DNA of resistant UV bacteria and archaea

Jorge Bresciano

I research on the hypothesis of a selection to less thymine dimmers content in the DNA of bacteria and archaea. The formation of the dymmers cause an important damage,so i count them in the genomes of resistant UV bacteria and i compare them with a group representing the total bacteria.

39

Sequence analysis of class 1 integron's integrase gene and the associated attI1 recombination site

María Paula Quiroga, Maximiliano Nardelli, María Soledad Ramírez, Daniela Centrón

We evaluated the variability of the type 1 integrase gene and the attI1 recombination site, plus the attI1's dispersion. We found various intI1 alleles among the nosocomial samples although the attI1 shows a remarkable stability, and that a specific portion of the attI1 is highly dispersed in the bacterial genomes.

40

Lifestyle, gene repertory and base composition bias in spirochetes

Natalia Rego, Martín Graña, Guillermo Lamolle, Fernando Alvarez-Valin, Hugo Naya

Spirochetes display different lifestyles even at the intragenus level. While highly variable, decrease of G+C content accompanying changes to a host-obligated cycle is not observed. We discuss this behaviour as related to modifications of the mutational bias associated to changes in DNA-repair enzyme repertory.

41

An easy way to incorporate phylogenetic uncertainty in the comparative model

Lucía Spangenberg, Natalia Rego, Hector Romero, Hugo Naya

We present an easy way to incorporate phylogenetic uncertainty in the comparative model. We run the mixed model of Lynch in a Bayesian manner for several sampled trees and integrate the different posterior distributions ("model-averaging"). No "true" evolutionary model has to be assumed, since the inference can be performed with trees constructed under different evolutionary.

42

Integrated in silico-wet biology approach for improving the annotation of Babesia bigemina perforin family

Romina Petrigh, Natalia Rego, Beatriz Valentini, Ignacio Echaide, Hugo Naya, Marisa Farber

Babesia bigemina is an apicomplexan haemoparasite that causes babesiosis in cattle. Currently, B. bigemina genome assembly and annotation is still in progress. In this work, we performed the annotation of a B. bigemina secreted protein family containing membrane- attack complex/ perforin (MACPF) - like domain using bioinformatic and biochemical tools.

43

A Combinatorial-Analytic Approach to Indel and Single Nucleotide Polymorphism Detection

Andrzej K. Brodzik

A new approach for the analysis of DNA sequences, based on combinatorial-analytic concepts, is proposed. In this approach the DNA sequence is represented by its subsampled version derived from the distribution of cyclic difference sets. The approach permits rapid identification of single nucleotide polymorphisms.

44

Molecular Evolution and Functional Divergence of Alcohol Dehydrogenases in Animals, Fungi and Plants

Thompson, C.E.; Freitas, L.B.; Salzano, F.M.

The alcohol dehydrogenase enzyme belongs to the large superfamily of medium- chain dehydrogenases/reductases, which have been characterized in animals, fungi, plants, protozoan, and bacteria. The phylogeny of 192 sequences of animals, fungi and plants were considered. Amino acid residues responsible for functional divergence between ADH types and among fungi, plant and animals were identified.

45

Discovery of a new conserved tandem motif upstream of outer membrane hemin transporters in alpha and beta-proteobacteria

Uriel Koziol, Vanesa Amarelle, Federico Rosconi, Francisco Noya, Mark R. O'Brian and Elena Fabiano

A conserved tandem motif is described upstream of genes that code for outer membrane hemin transporters in alpha and beta-proteobacteria. This motif is not found upstream of other iron uptake related genes, and its presence is associated with the presence of orthologs of the hmuP gene in the same genome.

46

Bioinformatic insight into eisosomes' molecular function

Agustina Olivera-Couto and Pablo S. Aguilar

Eisosomes are novel cellular structures that organize the plasma membrane. Not a single eisosomal protein bear an obvious structural domain. We have described the evolutionary distribution of different eisosomal proteins and predicted previously unrecognized protein domains of them. This study is highly valuable for the comprehension of eisosomes' molecular function.

47

Identifier (ID) elements inserted into non-coding regions of pol II-primary transcripts are not related to the regulation of tissue-specific gene expression in rat

Andrés Goldman, Evangelina González-López, Carlos A. Capoano and Adriana Geisinger

We hereby show that IDs, short interspersed repetitive sequences (SINEs) from rodents, that had a suspected role in brain-specific gene expression are equally distributed among brain-specific, other tissue-specific, and housekeeping genes. All the data indicate that IDs are randomly distributed and do not exert a role in tissue-specific gene regulation.

48

12D3 gene sequence conservation in Mexican isolates of Babesia bovis

Jocelin Perez, Javier Pérez, Patricia Vargas, Antonio Alvarez, Carmen Rojas, Julio V. Figueroa

Comparative analysis of the consensus nucleotide sequences obtained for the 12d3 alleles present in 19 out of 20 B. bovis Mexican isolates revealed a high degree of conservation (99% sequence identity) when compared to the 12d3 reference sequences from the Texan and Australian B. bovis isolates.

49

Initial Babesia bigemina gene identification by Expressed Sequence Tags analysis of the intraerythrocytic stage

Javier Perez, Patricia Vargas, Antonio Alvarez, Carmen Rojas, Julio V. Figueroa

Blast search for 1904 ESTs of Babesia bigemina showed 470 ESTs (267 clusters) had no significant sequence identity with Apicomplexan genes; 21 ESTs corresponded to 6 known B. bigemina antigen coding genes; 1285 ESTs (159 clusters) had identity with B. bovis coding genes; 112 ESTs corresponded to 59 non-Babesia genes.

Microbial Genomics and Metagenomics

50

A Hidden Markov Model that finds genes in Enterobacter DNA

Hebert HSG Soto

A hidden Markov model (HMM) has been developed to find protein coding genes in Enterobacter. DNA using Enterobacter genome DNA sequence from the EntSeq6 database maintained by Kenn Rudd. This HMM includes states that model the codons and their frequencies in Enterobacter genes, as well as the patterns found in the intergenic region, including repetitive.

51

Metagenomic analysis of bacteriophage present in the gut microbiota of monozygotic twins and their mothers

Alejandro Reyes, Matthew Haynes, Forest Rohwer and Jeffrey Gordon

Metagenomic methods were used to characterize the bacteriophage population in the gut microbiota of monozygotic adult twins and their mothers. Viral diversity is great within and between individuals and families. A few virotypes dominate a given time, allowing for viral genome assembly and assessment of viral proteins diversity.

52

Iron uptake systems in the grass endophyte Herbaspirillum seropedicaeZ67: structure and transport of an NRPS-siderophore

Federico Rosconi, Fabio Pedrosa, Emanuel de Souza and Elena Fabiano

Iron metabolism role in plant-endophytic bacteria interaction is poorly studied. Our aim is to evaluate the importance of siderophore-mediated iron uptake systems in the interaction between the endophyte Herbaspirillum seropedicae with the rice plant. By functional genomics we are studying genes implicated in siderophore biosynthesis, transport and regulation.

53

Characterization and identification of hydrolytic enzymes of potential interest in biofuel production by using metagenomics approaches

Cecilia Rodriguez, Daniela Senatore, Vanesa Amarelle, Adriana Peri, Uriel Koziol, Elena Fabiano, and Francisco Noya

An alternative to the production of biodiesel by transesterification, is the use of enzymes like esterases and lipases. The aim of this work is to characterize and identify hydrolytic enzymes for the production of biodiesel by using metagenomic approaches. We built a metagenomic library from intestines of termites.

54

16S rRNA gene diversity in cyanobacterial-bacterial mat consortia of King George Island, Maritime Antarctica

Cecilia Callejas, Emanuel M. de Souza, and Silvia Batista

Antarctic environments have been strongly affected by Climate Change. In this work we used a combination of molecular methods to describe microbial phylotypes present in different bacterial-cyanobacterial mats from King George Island, Maritime Antarctica. Our results can be used as a baseline to assess future impacts on Antarctic microbial communities.

55

Tuning a phylogenetic classification for metagenomic samples based on homology, using simulated data

Emiliano Pereira, Héctor Romero, Héctor Musto

Not given.

Computational Biomedicine

56

Gene Association Analysis of Gene Expression Data

Ronnie Alves, Domingo S. Rodriguez-Baena, Jesus S. Aguilar-Ruiz

Scalability achieved by efficient gene association mining methods does not imply biological soundness of the discovered association patterns and vice versa. We review the most relevant association mining strategies, as well as surrounding main issues when devising efficient and practical methods for gene association analysis (GAA).

57

Finding putative drug against H1N1 Virus (Influenza A virus) by computational virtual screening approach.

Ashwani Sharma, Ashish V. Tendulkar, Kuppili Raja Reddy, Pramod Wangikar

H1N1 virus genome has been sequenced and its neuraminidase protein structure was obtained by homology modeling. We docked modeled structure with several antiviral compounds from chemical & plant origin. Antiviral plant metabolites Hesperidin & Narirutin produced highest docking score as compare to known antiviral chemical compounds e.g Oseltamivir.

58

The dynamics of human ovarian reserve

T W Kelsey and W H B Wallace

We present a model for human ovarian reserve from conception to menopause. We combined eight histological studies into one dataset, and compared all biologically plausible models in terms of goodness of fit. The best fitting model suggests that 81% of the variance in reserve is due to age alone.

59

The lysosomal apoptosis signaling pathway is a complex biological network

Veronika Stoka, Boris Turk, Vito Turk

We firstly proposed the mechanism of action of lysosomal proteases, as activators of a cell death program, apoptosis. Hereby, using an integrative approach, we build up the signaling network. Interestingly, some unexpected features regarding the network topology were uncovered; thus providing an insight on novel potential therapeutic targets.

60

Theme-driven cancer survival analysis

Esteban Czwan, Benedikt Brors, David Kipling

In clinical oncology, the identification of deregulated biological pathways is useful to recognize therapeutic targets. We developed a "theme-driven" cancer survival methodology that screens hundreds of pathways or themes and tests associations with survival time. Our approach corrects for pitfalls of current methods, and reports novel GO-based and KEGG-based genesets that are predictive of survival.

61

Structural protein motifs that recognize damaged DNA

Juan José Cifuentes and Francisco Melo

In this work we present a database and a structural clustering of proteins and motifs that detect damaged DNA. We wanted to address if these proteins share common structural characteristics that explain how different proteins are able to recognize a single type of adduct.

62

In silico studies of sesquiterpene lactones with inhibitory activity of Nuclear Factor kappa B

Luis Alejandro Castro, Sara Aguilera Morales, Federico Iribarne Restuccia, Margot Paulino Zunini

A set of sesquiterpenic lactones which inhibit the transcription factor NF-kB, were studied. A QSAR model was created with the aim to predicting a putative antitumor action of similar compounds. A molecular docking was performed to calculate the NF-kB-lactones interaction energies and to obtain a graphical representation of the binding.

Infectious Diseases and Drug Target Discovery

63

Methodological developments based on genetic algorithm and normal mode analysis for performing protein-ligand and protein-protein docking simulations

Luis Scott, Perahia, David, Angelica Lima, Eric Phillot

The methods and the associated software under development combine different techniques that are Genetic Algorithms (GA), Molecular Dynamics (MD) and Normal Mode Analysis (NMA) [1] in order to apply them to the elucidation of the docking problem, by taking into account either local or global conformational changes of the protein.

64

Studies on the interactions of the enzyme InhA from Mycobacterium tuberculosis with small drug-like molecules

Ivani Pauli, Osmar Norberto de Souza, Luiz Augusto Basso, Diógenes Santiago Santos

InhA, a key enzyme of mycobacterium fatty acid elongation cycle, is an effective target to develop anti-tubercular agents. We report the identification of key InhA drug binding features, crucial to rational design of antitubercular drugs. We also established an efficient Virtual Screening protocol, able to identify new potential InhA inhibitors.

65

A based learning machine web system for selection medicinal plants of the cerrado with antimicrobial properties

Saulo França Amui, Lucas Junqueira de Freitas Morel, Ana Maria Soares Pereira, Silvana Giuliatti

Development a Web system capable of selecting best individuals of a specie of medicinal plant from cerrado with antimicrobial activity, using techniques of machine learning such as decision trees and neural networks, where the data of attributes and classes can be added and managed an online system.

66

Applying Model Trees on Flexible-Receptor Docking Experiments to select promising protein receptor snapshots

Karina S. Machado, Ana T. Winck, Duncan D. A. Ruiz, Osmar Norberto de Souza

The use of a series of receptor conformations is an approach to explore its flexibility in molecular docking, but it is extensively time-consuming. We propose a criterion of selection the most promising receptor conformations based on the receptor residues-ligands distances obtained from docking results applying the M5P model tree algorithm.

67

Designing and implementing chemoinformatic approaches in TDR Targets Database: linking genes to chemical compounds in tropical disease causing pathogens

María Paula Magariños, John Overington, Santiago Carmona, Dhanasekaran Shanmugam, Maria Doyle, Stuart Ralph, Greg Crowther, Christiane Hertz-Fowler, Solomon Nwaka, Matt Berriman, David Roos, Wes Van Voorhis, Fernán Agüero

TDR Targets (tdrtargets.org) is a database that associates gene information from human pathogens with genomic and functional information. In this work, information about 504,020 drug-like compounds was integrated into TDR Targets, providing users with the ability to search the database, and relate compounds with pathogen genes.

68

A Context-Based Preprocessing on Flexible-Receptor Docking Data

Ana T. Winck, Karina S. Machado, Osmar Norberto de Souza, Duncan D. A. Ruiz

This work is focused on producing machine-learning regression predictive models for flexible-receptor docking data. Our goal is to present how an efficient preprocessing step can improve the accuracy of the models. By analyzing the produced results, we assert that such strategy can produce more accurate models than an automatic approach.

69

A new method for multi-objective selection of molecular descriptors for QSAR/QSPR

Axel J. Soto, Rocío L. Cecchini, Gustavo E. Vazquez, Ignacio Ponzoni

We propose a two-phase methodology aimed at selecting relevant descriptors for QSAR models. Our technique was developed using multi-objective evolutionary algorithms. The main objective of our approach is that it be able to be used when many descriptors have to be considered regardless of the linear or nonlinear complexity of the QSAR model.

70

Alpha-Mannosyltransferase (pimA) from Mycobacterium tuberculosis H37Rv: molecular modeling, virtual screening and molecular dynamic studies

Luís Fernando Saraiva Macedo Timmers, Luiz Augusto Basso, Diógenes Santiago Santos and Walter Filgueira de Azevedo Jr.

Since 1952 no new drug has been discovered against tuberculosis, seeing that the search of new protein targets is an emergence to find potential inhibitors. Alpha-mannosyltransferase (PimA) has an important role in the cell wall biosynthesis, and is absent in humans, making this enzyme a potential target to virtual screening.

71

Integration and use of Schistosoma mansoni genomic data towards the identification of candidate therapeutic targets

Adhemar Zerlotini, Mark Heiges, Haiming Wang, Regina Coeli, Romulo Moraes, Anderson Dominitini, Jessica Kissinger, Guilherme Oliveira

Schistosomiasis is the second main cause of morbidity in the world among parasitic diseases, right after malaria. In the present research work, we describe how the construction of a genomic database was usefull to mining candidate therapeutic targets.

72

A mapping method for linking chemical compounds to biological and physicochemical properties in drug discovery

Axel J. Soto, Marc Strickert, Gustavo E. Vazquez

The new method presented here allows a mapping of the data vectors to a low-dimensional Euclidean space where distances of the projected points aim at being in maximal correlation with the target distances. This low-dimensional space represents an interesting preprocessing for cancelling noise and for improving predictions.

73

The effect of InhA flexibility in docking simulations with ethionamide and triclosan

Elisangela M. L. Cohen, Karina S. Machado, Osmar Norberto de Souza

The aim of this work is to contribute to a better understanding of the effect of receptor explicit flexibility on molecular docking. Hence we carried out docking experiments on a trajectory from molecular dynamics simulation, using as receptor InhA from M. Tuberculosis and as ligands ETH and TCL.

74

Peptide:MHC complexes reconstruction to infer binding affinity for the HLA-A*0201 allele

Maurício Menegatti Rigo, Dinler Amaral Antunes, Samuel Paulo Cibulski, Cassiana Chassot Fülber, Marialva Sinigaglia, José Artur Bogo Chies, Gustavo Fioravanti Vieira

Currently, a lot of immunoinformatics tools are available to help us to understand the mechanisms underlying the immune response. In this work we reconstruct peptide:MHC complexes through an approach developed by our group and we discuss the use of these complexes in a molecular dynamics approach.

75

The role of biosynthetic pathways as regulation mechanism of glycolysis in Trypanosoma brucei

Guido D. Núñez-Mujica, Antonio Parravano, Juan Luis Concepción

A new model of the bloodstream form of Trypanosoma brucei suggests that biosynthetic pathways could be playing a key role on glycolytic regulation, instead of the glycosomal membrane, as proposed by other authors.

76

Prediction of B-cell epitopes of dengue virus non-structural 1 (NS1) protein involved in dengue serotype specificity

Luiza A. Castro-Jorge, Benedito A. L. Fonseca

Early diagnosis and differentiation between DENV serotypes by NS1-ELISA are hard to be achieved. To identify DENV serotype specific B-cell epitopes in NS1, protein sequences were analyzed in B-cell epitope prediction programs. The non-conserved NS1 peptides identified may prove critical for developing a diagnostic test that can differentiate DENV serotypes.

77

An Integrative Bioinformatic Predictor of Protein Sub-Cellular Localisation in Malaria

Woodcroft BJ, Scanlon K, Doyle MA, Bailey J, Speed TP, Ralph SA

Bioinformatic prediction of protein sub-cellular localisation is normally attempted by only considering amino acid sequence information. Based on a comprehensive experimental localisation database, we have integrated a number of other genome-scale data types to predict protein localisation between seven different compartments of the malarial parasite P. falciparum.

78

Identification of Novel Epitopes of the Ebola Virus Towards Rational Vaccine Design, Virus Evolution, and Protein Conservation

Sophia Banton, Zvi Roth, Mirjana Pavlovic

Towards rational vaccine design, novel epitopes DAIVNAQPK and HNQDG were extracted from a 3D structure of an Ebola virus glycoprotein bound to a human antibody. Prediction servers identified DAIVNAQPK and numerous other epitopes. An Ebola nucleoprotein epitope -DYHKILTAG- is shown for the first time to contain a Eukaryotic protein fingerprint.

79

A Study of Molecular Descriptor to Rank Candidate Ligands to Inhibit the InhA Receptor

Christian V. Quevedo, Ana T. Winck, Karina S. Machado, Osmar Norberto de Souza, Duncan D. A. Ruiz

To reduce the time of ligand selection, we are motivated in applying molecular descriptors to filter the large amount of ligands available. We fell encouraged to develop a ligand similarity heuristic function using molecular descriptors to rank the most promising drug candidate molecules.

80

Computational prediction of putative inhibitor against Thymidine kinase enzyme of Herpes simplex virus (HSV-1): An approach for Drug discovery

Ashwani Sharma, Ashish V. Tendulkar, Pramod Wangikar

Herpes simplex virus type-1 causes several deadly diseases in humans. We predicted putative functional sites in its Thymidine kinase (3F0T) enzyme and docked with several antiviral compounds from chemical & plant origin. Antiviral plant metabolite Geraniin produced highest docking score as compare to known antiherpes chemical compound Acyclovir.

Functional Genomics and Systems Biology

81

Phenotypic Effects of Network Rewiring in Regulatory Hierarchies

Nitin Bhardwaj, Philip M. Kim and Mark B. Gerstein

We rearrange regulatory networks into hierarchies and superimpose the phenotypic effects of tampering with nodes and edges. We find that rewiring events that affect the upper levels have more dramatic effect on cell growth and location/type of change in modified hierarchies strongly correlates with the phenotypic effect.

82

wAtPIN: Weighted Arabidopsis thaliana Protein Interaction Network

Marcelo M. Brandão, Luiza L. B. Dantas, Marcio C. Silva-Filho

Protein-protein interactions (PPIs) constitute one of the most crucial conditions to sustain life in living organisms. wAtPIN is a friendly and easy-to-use tool that aggregates information on Arabidopsis thaliana PPIs, ontology, and sub-cellular localization, and might be a useful and reliable strategy to map protein-protein interactions in Arabidopsis.

83

Developmental aging in mammals: a systems biology analysis of epigenetic, development and senescence mechanisms

Bruno César Feltes, Joice de Faria Poloni, Diego Bonatto

By applying systems biology tools, we performed a study of Developmental Theory of Aging that so far has not been elucidated at molecular level. The protein-protein interaction models showed an interplay among epigenetic and senescence mechanisms, nutrient availability, and Hox expression in embryonic development.

84

Comparative genomics of lactation

Christophe Lefèvre, Karenza Menzies, Julie sharp, Kevin Nicholas

We are studying lactation in monotremes, marsupials and eutherians using comparative genomics and transcriptomics. A bioinformatics resource supports storage, retrieval, integration and analysis of the data generated. Examples of how this approach allows new insight into the evolution of milk proteins and the adaptation of mammary function will be presented.

85

Modeling gene expression: noise and cooperativity

Pablo S. Gutierrez, Laura Calcagni, Diana Monteoliva and Luis Diambra

We propose a mathematical model for gene expression noise. This model has several binding site forrnthe same transcriptional factor (TF) allowing to explore the relationship between TF cooperative rnbinding and noise.

86

Analysis of Trypanosoma cruzi gene expression in response to ionizing radiation using the DNA microarray technique

Priscila Grynberg, Danielle G. Passos-Silva, Roberto Hirata Jr., Andrea M. Macedo, Eduardo J. Neves, Carlos R. Machado, Daniella C. Bartholomeu, Glória R. Franco

Trypanosoma cruzi is an organism highly resistant to ionizing radiation. After a dose of 500 Gy of gamma radiation, the fragmented genomic DNA is gradually repaired in 48 hours. Transcripts profiles of epimastigotes irradiated or not were analyzed using the microarray technique and a specific pipeline developed for this purpose.

87

Differentially Expressed Genes in Microarray Analysis of Rheumatoid Arthritis Disease

Luiz Fernando M. Pignata, Nilson Nicolau Júnior, Flávia Sacilotto Donaires, Cristina M. Junta, Geraldo A. Passos, Silvana Giuliatti

The gene expression signature in patients with rheumatoid arthritis, obtained through the analysis of microarray data, showed the visible separation between patients and control subjects. Besides it was possible to characterize the presence of genes linked directly to other diseases such as type 2 diabetes.

88

A systems biology view about the role of nuclear melatonin receptors in neurogenesis

Joice de Faria Poloni, Bruno César Feltes, Diego Bonatto

The presence of nuclear melatonin receptors (NMR) and its association with neurogenesis are poorly described. By means of systems biology tools, it was possible to establish a relationship between NMR and early embryonic differentiation. The results indicated an intrinsic relationship between NMR and proteins necessary for neurogenesis.

89

Towards a taxonomy of centrality measures for gene expression data sets

Nicolás Pozo-Rojas, Mario Inostroza-Ponta, Pablo Moscato

The analysis of gene expression data sets is an important task in bioinformatics. Additionally, the study of centrality has been applied in several works on protein-protein interaction networks. This work presents the preliminary findings for the comparison of the results of centrality measures applied on gene expression networks.

90

Dose response alignment in a G protein coupled receptor pathway

Alan Bush, Ariel Chernomoretz, Rodrigo Laje, Alejandro Colman-Lerner

Dose response curves measured at several levels of the yeast pheromone pathway show good alignment (i.e. similar EC50 values). We quantitatively measured an early translocation event of the pathway, verified its alignment and behavior to specific perturbations. We implemented a model of the pathway to explain this system level property.

91

Gene Ontology guided clustering of gene expression profiles

Ariel Chernomoretz

Clustering techniques are usually employed to reveal common patterns of gene expression in DNA-microarray assays. We present a new clustering algorithm that integrates biological information about gene functions in the clustering procedure itself. The new methodology can simultaneously mine for meaningful structure in both, expression and functional spaces.

92

Quantitative study of mother-daughter asymmetry in Ace2 localization in yeast

Lucía Durrieu, Gunnar Cedersund, Alan Bush y Alejandro Colman-Lerner

Cell differentiation is often due to regulated localization of transcription factors. We have developed a method based on FRAP that allows us to determine nuclear import and export rates for single cells. We use this quantitative approach to study Ace2 asymmetric localization to the daughter nucleus of Saccharomyces cerevisiae.

93

RNA-binding proteins interactome in Trypanosoma cruzi

Henrique Preti, Alessandro Afornali, Newton de Medeiros Vidal, Christian Macagnan Probst, Marco Aurélio Krieger

Trypanosoma cruzi is a protozoan parasite causing Chagas Disease. One of its major aspects is control of gene expression occurs post-transcriptionally, and mRNA-binding proteins play a major role. We have build an ORFeome and are screening protein-protein interactions using a yeast-two hybrid approach to better understand the gene expression network.

94

Detecting Circadian Genes from Microarray

Carla Layana and Luis Diambra

By recourse of maximum entropy principle and information theory, we study the circadian rhythmic patterns underlying to the gene expression from Cyanobacterium Synechocystis. We propose that our procedure is a promising statistical tool for finding oscillatory expressed genes of any period in a microarray data set.

95

Animated visualization of biological processes

Tatiana Cartagena de Oliveira, Marcelo Cezar Pinto

Bioinformatics is a constant increasing area of study, especially in systems biology. The understanding of biological processes requires complex computational tools and a better way of visualizing its outputs. So we are devising an animated visualization tool to show the simulation output for biological processes available in SBML format.

96

Computational analysis of the Schistosoma mansoni genome for the identification of vaccine candidates

Rômulo Moraes, Jerônimo Ruiz, Adhemar Zerlotini, Guilherme Oliveira

Identification of vaccines candidates in the schistosoma mansoni genome using computational methods. In this work we performed the prediction of the antigens in the exposed proteins of human host. Selected candidates will be tested for immunoreactivity with sera from infection resistant humans and in vaccination challenge tests using animals.

97

Sunflower Functional Genome Database, a curated unigene database to support functional diversity studies in sunflower

Fernandez, P., Blesa, D., Príncipi, D., Fusari, C., Soria, M., Reynares, C., Angelone, L., Delfino, S., Conesa, A., Dopazo, J., Tapia, E., Heinz, R.A. and Paniego, N.

An oligonucleotide microarray and for the discovery of gene-rich SNPs were implemented, including abiotic and biotic gene expression profiling and association studies in sunflower. About 22,000 unigenes were annotated; a preliminary scan of the GO terms and KEGG annotations showed that the main biochemical pathways are represented.

98

Cell-fate decisions in mating pheromone stimulated yeast. A systems biology study

Ariel Chernomoretz, Luciana Bruno, Pablo Balenzuela, Rodrigo Laje, Rodrigo Baltanás, Elizabeth Kennedy, Alejandro Colman-Lerner

In type a S.cervisiae cells, alpha-factor pheromone triggers a fate decision to switch from normal growth to mating behavior. Based on a combined analysis of experimentation and modeling, we suggest a possible mechanism underlying this cell fate decision system as the interplay between the pheromone response pathway and the cell cycle.

99

Calculating metabolic responses from the stoichiometric network and optimization principles

Miguel Ponce de Leon, Hector Cancela, Luis Acerenza

Applying optimization criteria to the metabolism of Escherichia coli we were able to obtain four fundamental behaviors found experimentally: inhibition of respiration at high glucose concentrations, switch from fermentation to respiration when glucose decreases, induction of galactose utilization when the system is depleted from glucose and simultaneous consumption of glucose and galactose at low concentrations.

100

KinetoUTR: a tool for visualization and analyses of mRNA regulatory elements in kinetoplatids

Newton de Medeiros Vidal, Marco Aurélio Krieger, Christian Macagnan Probst

Gene expression regulation occurs post-transcriptionally in kinetoplastids. Understanding the interaction of proteins (RNA-binding proteins) and mRNAs (elements present in UTRs) is essential to provide a broader picture of post-transcriptional control networks. We describe KinetoUTR, a tool providing across genes and across genomes analyses and visualizations, helping identifying the cis-acting elements.

101

Understanding implications of tissue-specific codon usage in human

Tamara Fernández, Lucía Spangenberg, Ariel Chaparro, Natalia Rego, Mónica Marín, Hugo Naya

Bias in codon usage has been associated with gene regulation and protein folding. Tissue-specific codon usage implies that the same protein expressed in different tissues could have different conformations. We analyze expression data aiming to describe the patterns of tissue-codon usage and shed light on the forces underlying this phenomenon.

102

SPARC gene, identified in a multi-organism functional genomics approach, impairs wound healing in Drosophila melanogaster

Federico Prada, A. Chernomoretz, C. Alvarez-Fernandez, A. Llera, P. Wappner, E. Martín Blanco, O. Podhajcer

Our genomic approach identified SPARC as a gene phylogenetically conserved (using fly, mice and humanized skin) involved in wound healing. Further analysis in fly confirmed the importance of SPARC on the regulation of cell adhesion, shape changes and dorsal closure movements, and points to specific pathways linked to wound process.

103

Functional Genomic Data Visualisation for Biologist Users: Prototype Tools Enabling "Exploration-Style Analysis" of Malaria and Yeast Data

Dietlind L. Gerloff, Joanna Sharman, Richard Orton

Our tools MaGnET and YETI facilitate what we term "exploration-style" analysis of different types of functional genomic data for Plasmodium falciparum and Saccharomyces cerevisiae. Exploration-style analysis enables bench biologists to take data "browsing" to a next level, with modifiable selections and more visual and integrated displays than at other sites.