A comprehensive BAC resource

The Human Genome Project has generated extensive map and sequence data for a large number of Bacterial Artificial Chromosome (BAC) clones. In order to maximize the efficient use of the data and to minimize the redundant work for the research community, The Institute for Genomic Research (TIGR) comprehensive BAC resource (cBACr) (http://www.tigr.org/tdb/BacResource/BAC_resource_intro.html) was built as an expansion of the TIGR human BAC ends database. This resource collects, integrates and reports the information on library, maps, sequence, annotation and functions for each human and mouse BAC. The current database contains 635 016 human BACs and 265 617 mouse BACs that were characterized by various approaches, among which 22 705 human clones and 1000 mouse clones have sequence and annotation data.

Toward a successful multinational crop plant genome initiative

Plant genome research is needed as the foundation for an entirely new level of efficiency and success in the application of genetics and breeding to crop plants and products from crop plants. Genetic improvements in crop plants beyond current capabilities are needed to meet the growing world demand not only for more food, but also a greater diversity of food, higher-quality food, and safer food, produced on less land, while conserving soil, water, and genetic resources. Plant biology research, which is poised for dramatic advances, also depends fundamentally on plant genome research. The current Arabidopsis Genome Project has proved of immediate value to plant biology research, but a much greater effort is needed to ensure the full benefits of plant biology and especially plant genome research to agriculture. International cooperation is critical, both because genome projects are too large for any one country and the information forthcoming is of benefit to the world and not just the countries that do the work. Recent research on grass genomes has revealed that, because of extensive senteny and colinearity within linkage groups that make up the chromosomes, new information on the genome of one grass can be used to understand the genomes and predict the location of genes on chromosomes of the other grasses. Genome research applied to grasses as a group thereby can increase the efficiency and effectiveness of breeding for improvement of each member of this group, which includes wheat, corn, and rice, the world’s three most important sources of food.

The genome of Arabidopsis thaliana.

Arabidopsis thaliana is a small flowering plant that is a member of the family cruciferae. It has many characteristics--diploid genetics, rapid growth cycle, relatively low repetitive DNA content, and small genome size--that recommend it as the model for a plant genome project. The current status of the genetic and physical maps, as well as efforts to sequence the genome, are presented. Examples are given of genes isolated by using map-based cloning. The importance of the Arabidopsis project for plant biology in general is discussed.

Human genome report card.

Description based on: March 1993; title from cover.

1997 Delegates to the Second International Strategy Meeting on Human Genome Sequencing in Bermuda from Gert-Jan van Ommen

Photographs from the February 1997 Bermuda meeting. Courtesy of Gert-Jan van Ommen.

Beyond the human genome: microbes, metaphors and what it means to be human in an interconnected post-genomic world

Four years after the completion of the Human Genome Project, the US National Institutes for Health launched the Human Microbiome Project on 19 December 2007. Using metaphor analysis, this article investigates reporting in English-language newspapers on advances in microbiomics from 2003 onwards, when the word “microbiome” was first used. This research was said to open up a “new frontier” and was conceived as a “second human genome project”, this time focusing on the genomes of microbes that inhabit and populate humans rather than focusing on the human genome itself. The language used by scientists and by the journalists who reported on their research employed a type of metaphorical framing that was very different from the hyperbole surrounding the decipherment of the “book of life”. Whereas during the HGP genomic successes had been mainly framed as being based on a unidirectional process of reading off information from a passive genetic or genomic entity, the language employed to discuss advances in microbiomics frames genes, genomes and life in much more active and dynamic ways.

Protein markers of B. xylophilus Steiner & Buhrer, 1934 (Nickle, 1970) populations using quantitative proteomics and character compatibility.

The Pine Wood Nematode (PWN) Bursaphelenchus xylophilus is a severe forest pathogen in countries where it has been introduced and is considered a worldwide quarantine organism. In this study, protein markers for differentiating populations of this nematode were identified by studying differences among four selected Iberian and one American population. These populations were compared by quantitative proteomics (iTRAQ). From a total of 2860 proteins identified using the public database from the B. xylophilus genome project, 216 were unambiguous and significantly differentially regulated in the studied populations. Comparisons of their pairwise ratio were statistically treated and supported in order to convert them into discrete character states, suggesting that 141 proteins were not informative as population specific markers. Application of the Character Compatibility methodology on the remaining 75 proteins (belonging to families with different biological functions) excludes 27 which are incompatible among them. Considering only the compatible proteins, the method selects a subset of 30 specific unique protein markers which allowed the compared classification of the Iberian isolates. This approach makes it easier search for diagnostic tools and phylogenetic inference within species and populations of a pathogen exhibiting a high level of genetic diversity.

Manipulação do genoma humano: ética e direito

A biologia molecular tem fornecido as ferramentas básicas para os geneticistas se aprofundarem nos mecanismos moleculares que influem na variação das doenças. Deve-se destacar a responsabilidade científica e moral dos pesquisadores, uma vez que os cientistas devem imaginar as consequências morais da aplicação comercial de testes genéticos, já que esse fato envolve não só o indivíduo e suas famílias, mas toda a população. Além de ser preciso, também, fazer uma reflexão sobre como essas informações do genoma humano serão utilizadas, para o bem ou mal. O objetivo desta revisão foi trazer à luz do conhecimento dados sobre características éticas da aplicação da biologia molecular, relacionando-a com os direitos do ser humano. Após análise bibliográfica, pôde-se observar que o Projeto Genoma Humano gerou várias possibilidades, como identificação de genes associados a doenças com propriedades sinergísticas, mas modificando às vezes comportamentos ao intervir geneticamente no ser humano, trazendo benefícios ou malefícios sociais. O grande desafio é decidir o que a humanidade pretende em relação a este gigantesco salto.

Molecular markers and genetic diversity of Plasmodium vivax

Enhanced understanding of the transmission dynamics and population genetics for Plasmodium vivax is crucial in predicting the emergence and spread of novel parasite phenotypes with major public health implications, such as new relapsing patterns, drug resistance and increased virulence. Suitable molecular markers are required for these population genetic studies. Here, we focus on two groups of molecular markers that are commonly used to analyse natural populations of P. vivax. We use markers under selective pressure, for instance, antigen-coding polymorphic genes, and markers that are not under strong natural selection, such as most minisatellite and microsatellite loci. First, we review data obtained using genes encoding for P. vivax antigens: circumsporozoite protein, merozoite surface proteins 1 and 3α, apical membrane antigen 1 and Duffy binding antigen. We next address neutral or nearly neutral molecular markers, especially microsatellite loci, providing a complete list of markers that have already been used in P. vivax populations studies. We also analyse the microsatellite loci identified in the P. vivax genome project. Finally, we discuss some practical uses for P. vivax genotyping, for example, detecting multiple-clone infections and tracking the geographic origin of isolates.

No-match ORESTES explored as tumor markers

Sequencing technologies and new bioinformatics tools have led to the complete sequencing of various genomes. However, information regarding the human transcriptome and its annotation is yet to be completed. The Human Cancer Genome Project, using ORESTES (open reading frame EST sequences) methodology, contributed to this objective by generating data from about 1.2 million expressed sequence tags. Approximately 30 of these sequences did not align to ESTs in the public databases and were considered no-match ORESTES. On the basis that a set of these ESTs could represent new transcripts, we constructed a cDNA microarray. This platform was used to hybridize against 12 different normal or tumor tissues. We identified 3421 transcribed regions not associated with annotated transcripts, representing 83.3 of the platform. The total number of differentially expressed sequences was 1007. Also, 28 of analyzed sequences could represent noncoding RNAs. Our data reinforces the knowledge of the human genome being pervasively transcribed, and point out molecular marker candidates for different cancers. To reinforce our data, we confirmed, by real-time PCR, the differential expression of three out of eight potentially tumor markers in prostate tissues. Lists of 1007 differentially expressed sequences, and the 291 potentially noncoding tumor markers were provided.

Wolbachia genomes and the many faces of symbiosis

How could scientists working on the pathogenesis of filarial diseases, speciation and parthenogenesis in insects, sex-ratio deviations in crustaceans, pest control, and the evolution of bacterial genomes be united? How could a common research project attract the interest of these scientists? How could parasitology be made even more multi-disciplinary? Two workshops organized by New England Biolabs Inc. (Beverly, MA, USA) provide a simple answer to these questions: studying the genomes of Wolbachia endosymbionts.

Annexin A1 subcellular expression in laryngeal squamous cell carcinoma

Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine-kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim was to investigate subcellular patterns of immunohistochemical expression of ANXA1 in neoplastic and non-neoplastic samples from patients with laryngeal squamous cell carcinomas (LSCC), to elucidate the role of ANXA1 in laryngeal carcinogenesis. Serial analysis of gene expression experiments detected reduced expression of ANXA1 gene in LSCC compared with the corresponding non-neoplastic margins. Quantitative polymerase chain reaction confirmed ANXA1 low expression in 15 LSCC and eight matched normal samples. Thus, we investigated subcellular patterns of immunohistochemical expression of ANXA1 in 241 paraffin-embedded samples from 95 patients with LSCC. The results showed ANXA1 down-regulation in dysplastic, tumourous and metastatic lesions and provided evidence for the progressive migration of ANXA1 from the nucleus towards the membrane during laryngeal tumorigenesis. ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases.

A solution for estimates in software development projects

The Corporate world is becoming more and more competitive. This leads organisations to adapt to this reality, by adopting more efficient processes, which result in a decrease in cost as well as an increase of product quality. One of these processes consists in making proposals to clients, which necessarily include a cost estimation of the project. This estimation is the main focus of this project. In particular, one of the goals is to evaluate which estimation models fit the Altran Portugal software factory the most, the organization where the fieldwork of this thesis will be carried out. There is no broad agreement about which is the type of estimation model more suitable to be used in software projects. Concerning contexts where there is plenty of objective information available to be used as input to an estimation model, model-based methods usually yield better results than the expert judgment. However, what happens more frequently is not having this volume and quality of information, which has a negative impact in the model-based methods performance, favouring the usage of expert judgement. In practice, most organisations use expert judgment, making themselves dependent on the expert. A common problem found is that the performance of the expert’s estimation depends on his previous experience with identical projects. This means that when new types of projects arrive, the estimation will have an unpredictable accuracy. Moreover, different experts will make different estimates, based on their individual experience. As a result, the company will not directly attain a continuous growing knowledge about how the estimate should be carried. Estimation models depend on the input information collected from previous projects, the size of the project database and the resources available. Altran currently does not store the input information from previous projects in a systematic way. It has a small project database and a team of experts. Our work is targeted to companies that operate in similar contexts. We start by gathering information from the organisation in order to identify which estimation approaches can be applied considering the organization’s context. A gap analysis is used to understand what type of information the company would have to collect so that other approaches would become available. Based on our assessment, in our opinion, expert judgment is the most adequate approach for Altran Portugal, in the current context. We analysed past development and evolution projects from Altran Portugal and assessed their estimates. This resulted in the identification of common estimation deviations, errors, and patterns, which lead to the proposal of metrics to help estimators produce estimates leveraging past projects quantitative and qualitative information in a convenient way. This dissertation aims to contribute to more realistic estimates, by identifying shortcomings in the current estimation process and supporting the self-improvement of the process, by gathering as much relevant information as possible from each finished project.

MR MAQ: algorisme de Read Mapping utilitzant la plataforma Hadoop

L’èxit del Projecte Genoma Humà (PGH) l’any 2000 va fer de la “medicina personalitzada” una realitat més propera. Els descobriments del PGH han simplificat les tècniques de seqüenciació de tal manera que actualment qualsevol persona pot aconseguir la seva seqüència d’ADN complerta. La tecnologia de Read Mapping destaca en aquest tipus de tècniques i es caracteritza per manegar una gran quantitat de dades. Hadoop, el framework d’Apache per aplicacions intensives de dades sota el paradigma Map Reduce, resulta un aliat perfecte per aquest tipus de tecnologia i ha sigut l’opció escollida per a realitzar aquest projecte. Durant tot el treball es realitza l’estudi, l’anàlisi i les experimentacions necessàries per aconseguir un Algorisme Genètic innovador que utilitzi tot el potencial de Hadoop.