Avances de la bioinformática en Costa Rica: vista retrospectiva y perspectivas / Bioinformatics advances in Costa Rica: retrospective view and perspectives

Resumen Introducción: La disciplina científica de la bioinformática tiene el potencial de generar aplicaciones innovadoras para las sociedades humanas. Costa Rica, pequeña en tamaño y población en comparación con otros países de América Latina, ha ido adoptando la disciplina de manera progresiva. El reconocer los avances permite determinar hacia dónde puede dirigirse el país en este campo, así como su contribución a la región latinoamericana. Objetivo: En este manuscrito se reporta evidencia de la evolución de la bioinformática en Costa Rica, para identificar debilidades y fortalezas que permitan definir acciones a futuro. Métodos: Se realizaron búsquedas en bases de datos de publicaciones científicas y repositorios de secuencias, así como información de actividades de capacitación, redes, infraestructura, páginas web y fuentes de financiamiento. Resultados: Se observan avances importantes desde el 2010, incluyendo un aumento en oportunidades de entrenamiento y número de publicaciones, aportes significativos a las bases de datos de secuencias y conexiones por medio de redes. Sin embargo, ciertas áreas, como la masa crítica y la financiación requieren más desarrollo. La comunidad científica y sus patrocinadores deben promover la investigación basada en bioinformática, invertir en la formación de estudiantes de posgrado, aumentar la formación de profesionales, crear oportunidades laborales para carreras en bioinformática y promover colaboraciones internacionales a través de redes. Conclusiones: Se sugiere que para experimentar los beneficios de las aplicaciones de la bioinformática se deben fortalecer tres aspectos clave: la comunidad científica, la infraestructura de investigación y las oportunidades de financiamiento. El impacto de tal inversión sería el desarrollo de proyectos ambiciosos pero factibles y colaboraciones extendidas dentro de la región latinoamericana. Esto permitiría realizar contribuciones significativas para abordar los desafíos globales y la aplicación de nuevos enfoques de investigación, innovación y transferencia de conocimiento para el desarrollo de la economía, dentro de un marco de ética de la investigación.

Abstract Introduction: The scientific discipline of bioinformatics has the potential to generate innovative applications for human societies. Costa Rica, small in size and population compared to other Latin American countries, has been progressively adopting the discipline. Recognizing progress makes it possible to determine where the country can go in this field, as well as its contribution to the Latin American region. Objective: This manuscript reports evidence of the evolution of bioinformatics in Costa Rica, to identify weaknesses and strengths allowing future actions plans. Methods: We searched databases of scientific publications and sequence repositories, as well as information on training activities, networks, infrastructure, web pages and funding sources. Results: Important advances have been observed since 2010, such as increases in training opportunities and the number of publications, significant contributions to the sequence databases and connections through networks. However, areas such as critical mass and financing require further development. The scientific community and its sponsors should promote bioinformatics-based research, invest in graduate student training, increase professional training, create career opportunities in bioinformatics, and promote international collaborations through networks. Conclusions: It is suggested that in order to experience the benefits of bioinformatics applications, three key aspects must be strengthened: the scientific community, the research infrastructure, and funding opportunities. The impact of such investment would be the development of ambitious but feasible projects and extended collaborations within the Latin American region and abroad. This would allow significant contributions to address global challenges and the implementation of new approaches to research, innovation and knowledge transfer for the development of the economy, within an ethics of research framework.

Análisis de las polihidroxialcanoato sintasas (PhaC1 y PhaC2) en una cepa de Pseudomonas fluorescens IBUN S1602, aislada en suelos colombianos / Analysis of polyhydroxyalkanoate synthases (PhaC1 and PhaC2) in a strain of Pseudomonas fluorescens IBUN S1602 isolated from Colombian soil

La cepa Pseudomonas fluorescens IBUN S1602 conforma el grupo de aislamientos provenientes de suelos colombianos de caña de azúcar, que acumula polihidrioxialcanoato (PHA), fue seleccionada como promisoria para escalamiento comercial por tener afinidad por sustratos alternativos y económicos como el glicerol, aceites usados, suero de leche, entre otros. Dada la importancia de la enzima sintasa en la síntesis de los PHAs, en el presente trabajo se realizó el análisis molecular de los genes phaC1 y phaC2 que codifican las enzimas sintasas tipo II (PhaC1 y PhaC2). Para la obtención de los amplímeros requeridos en la secuenciación, se utilizó la técnica de PCR bajo condiciones estandarizadas para iniciadores diseñados reportados en las bases de datos. Se identificaron dos fragmentos de 1680 pb y 1683 pb correspondientes a phaC1 y phaC2. El análisis comparativo de las secuencias proteicas resultantes de estos genes demuestra que la sintasa IBUN S1602 contiene la región α/β hidrolasa y 8 residuos de aminoácidos conservados, que son características de las sintasas examinadas a nivel mundial. Se analizó la estructura enzimática a nivel primario y se predijo la secundaria. Se concluyó que las sintasas de la cepa Pseudomonas fluorescens IBUN S1602 presentan alta homología con las sintasas tipo II que se reportan para Pseudomonas. Los resultados obtenidos contribuyen al entendimiento básico de la biosíntesis de PHA, la cual permitirá, en un futuro, el aumento de la calidad de PHA debida a la modulación del nivel de sintasa que se exprese en un organismo recombinante, con el fin de variar el peso molecular del biopolímero, propiedad esencial en el estudio de aplicaciones industriales.

The strain Pseudomonas fluorescens IBUN S1602 forms the group of isolates from colombian sugarcane soil´s, which accumulates polyhydroxyalkanoate biopolymer (PHA) and was selected as promising for commercial scale by having affinity for economic and alternative substrates such as glycerol, oils, whey, among others. Given the importance of the synthase enzyme in the synthesis of PHAs, was realized the molecular analysis of genes phaC1 and phaC2 which encode type II synthases (PhaC1 y PhaC2). To obtain the amplimers required in the sequencing, was used the PCR technique under standardized conditions for primers designed based on the updated review in databases. Were identified two fragments of 1680 bp and 1683 bp for phaC1 and phaC2. Comparative analysis of the resulting protein sequences of these genes shows that the IBUN S1602 synthases containing the region α/β hydrolase and 8 conserved amino acid residues that are characteristic of synthases examined worldwide. Enzyme structure was analyzed at the primary level and was predicted the secondary. It is concluded that synthase strain Pseudomonas fluorescens IBUN S1602 has high homology with type II synthases that are reported for Pseudomonas. The results contribute to basic understanding of the biosynthesis of PHA, and will allow in the future, increasing the quality of PHA due to modulation of the level of synthase is expressed in a recombinant organism, in order to vary the weight molecular biopolymer, an essential property in the study of industrial applications.

Nanoinformatics: an emerging area of information technology at the intersection of bioinformatics, computational chemistry and nanobiotechnology

After the progress made during the genomics era, bioinformatics was tasked with supporting the flow of information generated by nanobiotechnology efforts. This challenge requires adapting classical bioinformatic and computational chemistry tools to store, standardize, analyze, and visualize nanobiotechnological information. Thus, old and new bioinformatic and computational chemistry tools have been merged into a new sub-discipline: nanoinformatics. This review takes a second look at the development of this new and exciting area as seen from the perspective of the evolution of nanobiotechnology applied to the life sciences. The knowledge obtained at the nano-scale level implies answers to new questions and the development of new concepts in different fields. The rapid convergence of technologies around nanobiotechnologies has spun off collaborative networks and web platforms created for sharing and discussing the knowledge generated in nanobiotechnology. The implementation of new database schemes suitable for storage, processing and integrating physical, chemical, and biological properties of nanoparticles will be a key element in achieving the promises in this convergent field. In this work, we will review some applications of nanobiotechnology to life sciences in generating new requirements for diverse scientific fields, such as bioinformatics and computational chemistry.

Necesidad de un centro nacional de bioinformática y biología computacional para Colombia / The need for a Colombian bioinformatics and computational biology centre

Los principales y más revolucionarios avances de la biología en este siglo se han derivado de la información proveniente de genomas completos de diferentes organismos. Los descubrimientos que se derivan de la genómica están generando un nuevo paradigma en la biología, sustituyendo la era de la biología centrada en los genes por aquella centrada en los genomas. Este nuevo concepto es base para desarrollos de gran potencial e impacto social en diferentes áreas como la medicina, la agricultura y la industria. El éxito en el desarrollo de métodos de última generación para la secuenciación de genomas, la proteómica y todas las “omicas”, ha contribuido al surgimiento de nuevas posibilidades para el análisis de la enorme cantidad de datos que se están generando mediante el uso de herramientas computacionales, dando origen a una nueva rama de estudio conocida como bioinformática o biología computacional.Este trabajo hace una revisión general del desarrollo de la bioinformática y la biología computacional en Colombia. Inicialmente, a modo de comparación, describimos el desarrollo de esta ciencia en otros países latinoamericanos que son reconocidos en el área. Finalmente, se discuten los principales aspectos que van a jugar un papel importante en el futuro de esta ciencia en nuestro país, y que además justifican la necesidad de crear un centro nacional de bioinformática y biología computacional.

The main, most revolutionary advances in biology during this century have arisen from information being provided from revealing different organisms’ complete genomes. The discoveries deriving from genomics are leading to a new paradigm in biology, the era of gene-centred biology being substituted for that centred on genomes. Such new concepts represent the basis for developments with great potential and social impact in different areas such as medicine, agriculture and industry. The successful development of latestgeneration methods for genome sequencing, proteomics and all the other “-omics” has contributed towards an enormous amount of genetic data being produced that needs to be analyzed using computational tools. This has led to the development of a new area called bioinformatics or computational biology.The present work gives a general overview of the development of bioinformatics and computational biology in Colombia. The justification for the establishment of a National ioinformatics and computational biology centre is discussed, as well as some aspects that will be crucial for developing this science in Colombia.

Construção de uma biblioteca de módulos para utilização na composição de workflows para filogenia / Construction of a library of modules for use in the composition of workflows for phylogeny

Com o advento da era pós-genômica, ocorreu uma explosão de informações onde inúmeras descobertas geraram grande quantidade de dados biológicos, que para serem analisados, necessitavam da cooperação de várias áreas de conhecimento. Inicialmente, as atividades de análises destes dados são suportadas por programas que constituem um fluxo de trabalho, baseado em scripts, que normalmente são executados por linha de comando, obrigando os seus usuários a terem domínio de algoritmos e lógica de programação. Tais scripts auxiliam muito na entrada, processamento e resultado final da análise, mas ainda apresentam dificuldades em interferir, coletar e armazenar dados ao longo de sua execução. Além disso, dependendo da especificidade do script, o seu uso pode ser muito complexo, em função da dificuldade da implementação, manutenção e reuso. Também, neste tipo de ambiente, o registro de execução das atividades do fluxo, da origem dos dados utilizados e das transformações aplicadas aos dados, geralmente, não são mantidos. Para tanto, tem havido o crescente uso de workflows científicos na execução e condução de experimentos científicos. Os workflows científicos pressupõem a resolução de problemas científicos através das técnicas de composição do fluxo de atividades, onde os passos normalmente são compostos por programas de bioinformática que recebem, processam e geram um conjunto de dados que podem ser repassados aos demais passos do workflow. Toda a estrutura de desenvolvimento e execução desses workflows é apoiada por sistemas específicos, conhecidos como Sistemas de Gerenciamento de Workflows Científicos (SGWfC), que possuem seus próprios mecanismos de gerência e linguagem. Considerando as vantagens de uso dos SGWfC no cenário da Bioinformática, este trabalho apresenta o workflow científico para reconstrução filogenética denominado PHYLO...

With the advent of post-genomic era, there was an explosion of information where many discoveries have generated large amounts of biological data, which, to be analyzed, needed the cooperation of various fields of knowledge. Initially, the to industrial activities of analysis of these data are supported by programs that constitute the workflow, based on scripts, that normally run from command line, forcing users to algorithms and programming logic. Such scripts help much the input, processing and outcome of the analysis, but still present difficulties for usersto interfere, collect and store data throughout their implementation. Also, according to the specific use of the script, it can be very complex, depending on the difficultyof implementation, maintenance and reuse. Also, in this type of environment, the registration of the execution of the activities of the flow, the source of data use d and the transformations applied to the data are generally not retained. For these, there has been the growing use of scientific workflows for the implementation and execution of scientific experiments. Scientific workflows assume scientificproblems solving through techniques of composition of the flow of activities, where the steps are usually composed of bioinformatics programs that receive, process and generate a data set that can be passed on to other steps of the workflow. The structure of development and implementation of these workflows is supported by specific systems, known as Scientific Workflows Management Systems (SGWfC), which have their own management mechanisms and language. Considering theadvantages of using the scenario SWfMS in the scientific bioinformatics, this work presents the scientific workflow PHYLO for phylogenetic reconstruction...

Caracterização de proteínas MAPKs e MKPs no Genoma de Schistosoma mansoni: uma abordagem in silico e experimental

Pouco se sabe a respeito dos mecanismos de transdução de sinal no parasito Schistosoma mansoni. A identificação e caracterização dos mecanismos e das moléculas envolvidas em vias de transdução de sinal são essenciais para se entender a biologia do parasito e interações hospedeiro-parasito. As proteínas MAPK (Mitogen-activated protein kinases) desempenham um importante papel na transdução de sinais extracelulares, controlando vários mecanismos celulares essências. As MKPs são o principal grupo de proteína fosfatases que controlam a magnitude e a duração da ativação das proteínas MAPK. Até o presente momento, nenhuma proteína da família das MAPKs ou proteínas MKPs havia sido detalhadamente caracterizada no parasito S. mansoni. Foi realizada uma análise in silico. abragente da versão 3.1 do genoma de S. mansoni utilizando diferentes abordagens de bioinformática, incluindo buscas por similaridade de seqüências realizadas com o algoritmo blast ou com modelos ocultos de Markov (HMM) especificamente elaborados e construídos para identificação de MAPKs e MKPs. Complementarmente foi realizada a anotação manual dos genes que apresentaram hits positivos para proteínas MAPK e MKP utilizando o programa Artemis para integrar as anotações.

Com base nesses resultados quatro proteínas foram selecionadas para posterior validação experimental: uma proteína ERK (SmMAPK1), uma proteína JNK (SmMAPK2) e duas proteínas fosfatase de dupla especificidade (SmMKP1e SmMKP2). Análises in silico revelaram ainda que os aminoácidos importantes para a funcionalidade das proteínas estão conservados. Nas MAPKs os resíduos dos domínios CD e ED, essenciais para o reconhecimento dos ativadores, substratos e desativadores, estão conservados. Nas fosfatases, o sítio de ligação as MAPKs está presente e apresenta os aminoácidos essenciais para a interação entre as proteínas. O cDNA de SmMAPK1, SmMAPK2, SmMKP1 e SmMKP2 está presente em todas as fases de desenvolvimento do parasito. E, em SmMKP1 observamos grande quantidade de transcrito em miracídio e também a presença de ortólogos a SmMKP1 em diversas espécies do gênero Schistosoma. As proteínas foram expressas em fusão a GST utilizando vetor de expressão pGEX. O teste de solubilidade mostrou que SmMAPK1, SmMKP1 e SmMKP2 estão presente na fase insolúvel, provavelmente em corpos de inclusão. Esse trabalho enfatiza a importância de se integrar projetos de sequenciamento do genoma, predição de proteínas, anotação manual dos genes e validação experimental para a identificação de proteínas alvo para o desenvolvimento de novas drogas

The Current Trend of Avian Influenza Viruses in Bioinformatics Research / 예방의학회지

OBJECTIVES: Since the first human infection from avian influenza was reported in Hong Kong in 1997, many Asian countries have confirmed outbreaks of highly pathogenic H5N1 avian influenza viruses. In addition to Asian countries, the EU authorities also held an urgent meeting in February 2006 at which it was agreed that Europe could also become the next target for H5N1 avian influenza in the near future. In this paper, we provide the general and applicable information on the avian influenza in the bioinformatics field to assist future studies in preventive medicine. METHODS: We introduced some up-to-date analytical tools in bioinformatics research, and discussed the current trends of avian influenza outbreaks. Among the bioinformatics methods, we focused our interests on two topics: attern analysis using the secondary database of avian influenza, and structural analysis using the molecular dynamics simulations in vaccine design. RESULTS: Use of the public genome databases available in the bioinformatics field enabled intensive analysis of the genetic patterns. Moreover, molecular dynamic simulations have also undergone remarkable development on the basis of the high performance supercomputing infrastructure these days. CONCLUSIONS: The bioinformatics techniques we introduced in this study may be useful in preventive medicine, especially in vaccine and drug discovery.

Bioinformatics: perspectives for the future

I give here a very personal perspective of Bioinformatics and its future, starting by discussing the origin of the term (and area) of bioinformatics and proceeding by trying to foresee the development of related issues, including pattern recognition/data mining, the need to reintegrate biology, the potential of complex networks as a powerful and flexible framework for bioinformatics and the interplay between bio- and neuroinformatics. Human resource formation and market perspective are also addressed. Given the complexity and vastness of these issues and concepts, as well as the limited size of a scientific article and finite patience of the reader, these perspectives are surely incomplete and biased. However, it is expected that some of the questions and trends that are identified will motivate discussions during the IcoBiCoBi round table (with the same name as this article) and perhaps provide a more ample perspective among the participants of that conference and the readers of this text.

Public sphere and the sustainability of the bioinformatics promise

The literature about genomics and bioinformatics achievements in high-impact journals such as Nature and Science has raised disproportionate expectations amongst the general public about fast and revolutionary drugs and breakthroughs in biomedicine. However, the yield obtained by database mining activities has been modest, as reported in the February 2001 issues of these journals featuring the completion of human genome draft sequences by the Human Genome Project Consortium and the company Celera. I have compared changes in rethoric employed by molecular biologists in 2001 and in April 2003, when the final sequence was announced. The comparison suggests that researchers are concerned about the sustainability of society’s investment in this field, though not explicitly.