The Bgee suite: integrated curated expression atlas and comparative transcriptomics in animals.

Bgee is a database to retrieve and compare gene expression patterns in multiple animal species, produced by integrating multiple data types (RNA-Seq, Affymetrix, in situ hybridization, and EST data). It is based exclusively on curated healthy wild-type expression data (e.g., no gene knock-out, no treatment, no disease), to provide a comparable reference of normal gene expression. Curation includes very large datasets such as GTEx (re-annotation of samples as 'healthy' or not) as well as many small ones. Data are integrated and made comparable between species thanks to consistent data annotation and processing, and to calls of presence/absence of expression, along with expression scores. As a result, Bgee is capable of detecting the conditions of expression of any single gene, accommodating any data type and species. Bgee provides several tools for analyses, allowing, e.g., automated comparisons of gene expression patterns within and between species, retrieval of the prefered conditions of expression of any gene, or enrichment analyses of conditions with expression of sets of genes. Bgee release 14.1 includes 29 animal species, and is available at https://bgee.org/ and through its Bioconductor R package BgeeDB.

Lymphopenia combined with low TCR diversity (divpenia) predicts poor overall survival in metastatic breast cancer patients.

Lymphopenia (< 1Giga/L) detected before initiation of chemotherapy is a predictive factor for death in metastatic solid tumors. Combinatorial T cell repertoire (TCR) diversity was investigated and tested either alone or in combination with lymphopenia as a prognostic factor at diagnosis for overall survival (OS) in metastatic breast cancer (MBC) patients. The combinatorial TCR diversity was measured by semi quantitative multi-N-plex PCR on blood samples before the initiation of the first line chemotherapy in a development (n = 66) and validation (n = 67) MBC patient cohorts. A prognostic score, combining lymphocyte count and TCR diversity was evaluated. Univariate and multivariate analyses of prognostic factors for OS were performed in both cohorts. Lymphopenia and severe restriction of TCR diversity called "divpenia" (diversity ≤ 33%) were independently associated with shorter OS. Lympho-divpenia combining lymphopenia and severe divpenia accurately identified patients with poor OS in both cohorts (7.6 and 10.6 vs 24.5 and 22.9 mo). In multivariate analysis including other prognostic clinical factors, lympho-divpenia was found to be an independent prognostic factor in the pooled cohort (p = 0.005) along with lack of HER2 and hormonal receptors expression (p = 0.011) and anemia (p = 0.009). Lympho-divpenia is a novel prognostic factor that will be used to improve quality of MBC patients' medical care.

vHOG, a multispecies vertebrate ontology of homologous organs groups.

MOTIVATION: Most anatomical ontologies are species-specific, whereas a framework for comparative studies is needed. We describe the vertebrate Homologous Organs Groups ontology, vHOG, used to compare expression patterns between species. RESULTS: vHOG is a multispecies anatomical ontology for the vertebrate lineage. It is based on the HOGs used in the Bgee database of gene expression evolution. vHOG version 1.4 includes 1184 terms, follows OBO principles and is based on the Common Anatomy Reference Ontology (CARO). vHOG only describes structures with historical homology relations between model vertebrate species. The mapping to species-specific anatomical ontologies is provided as a separate file, so that no homology hypothesis is stated within the ontology itself. Each mapping has been manually reviewed, and we provide support codes and references when available. AVAILABILITY AND IMPLEMENTATION: vHOG is available from the Bgee download site (http://bgee.unil.ch/), as well as from the OBO Foundry and the NCBO Bioportal websites. CONTACT: bgee@isb-sib.ch; frederic.bastian@unil.ch.

Homolonto: generating homology relationships by pairwise alignment of ontologies and application to vertebrate anatomy.

MOTIVATION: The anatomy of model species is described in ontologies, which are used to standardize the annotations of experimental data, such as gene expression patterns. To compare such data between species, we need to establish relations between ontologies describing different species. RESULTS: We present a new algorithm, and its implementation in the software Homolonto, to create new relationships between anatomical ontologies, based on the homology concept. Homolonto uses a supervised ontology alignment approach. Several alignments can be merged, forming homology groups. We also present an algorithm to generate relationships between these homology groups. This has been used to build a multi-species ontology, for the database of gene expression evolution Bgee. AVAILABILITY: download section of the Bgee website http://bgee.unil.ch/

Evolutionary genomics of nuclear receptors: from twenty-five ancestral genes to derived endocrine systems.

Bilaterian animals are notably characterized by complex endocrine systems. The receptors for many steroids, retinoids, and other hormones belong to the superfamily of nuclear receptors, which are transcription factors regulating many aspects of development and homeostasis. Despite a diversity of regulatory mechanisms and physiological roles, nuclear receptors share a common protein organization. To obtain the broad picture of bilaterian nuclear hormone receptor evolution, we have characterized the complete set of nuclear receptor genes from nine animal genome sequences and analyzed it in a phylogenetic framework. In addition, expressed sequence tags from key lineages with no available genome sequence were also searched. This allows us to date the evolutionary events that led from an ancestral nuclear receptor gene, in an early metazoan, to present day diversity. We show that there were approximately 25 nuclear receptor genes in Urbilateria, the ancestor of bilaterians, at which point the fundamental diversity of the subfamily was already established. Surprisingly, differential gene loss played an important role in the evolution of different nuclear receptor sets in bilaterian lineages. The nuclear receptor distribution was also shaped by periods of gene duplication, essentially in vertebrates, as well as a lineage-specific duplication burst in nematodes. Our results imply that the genes for major receptors such as steroid receptors or thyroid hormone receptors were present in Urbilateria.

Budd-Chiari syndrome associated with inferior vena caval obstruction: surgical treatment; cavo-or meso-atrial shunt

Em 6 anos, 17 pacientes foram submetidos à derivaçäo entre o sistema mesentérico-esplenoportal (15 vezes) ou o sistema cava inferior com anastomose mesentérico ou portocava (duas vezes) e o átrio direito. O grupo era composto de nove homens e oito mulheres; entre estes, 14 eram adultos com idades de 19 a 61 anos e três crianças, com idades de 2 a 5 anos. Com uma exceçäo, todos apresentavam ascite. Três pacientes foram operados na urgência devido: hemorragia por ruptura de varizes do fundo gástrico, síndrome hepato-renal e um por aumento súbito das transaminases (cinco vezes o normal). As lesöes centrolobulares foram confirmadas, em todos os casos, através de biopsia pré-operatória e/ou per-operatória. A oclusäo das veias sub-hepáticas foi demonstrada em todos os casos por, no mínimo, dois dos exames seguintes: ultra-sonografia, angio tomografia, flebografia supra-hepática, ou portografia transhepática. A cavografia demonstrou obstruçäo completa de veia cava em oito casos e incompleta em nove, acarretando hipertensäo de veia cava, com gradiente porto-cava variando de -6a +6mm de mercúrio. Nas anastomoses utilizou-se próteses de politetrafluor e tileno (Gore-Tex), com uma única exceçäo, onde foi utilizada prótese de dacron. As próteses foram passadas sete vezes à frente do fígado e dez vezes por trás do lobo esquerdo. A anastomose foi feita dez vezes com a face inferior do átrio direito, abordando nove vezes por frenotomia e uma vez por esternotomia; seis vezes com face anterior do átrio direito abordado por esternotomia; e uma vez com a veia cava superior intra-pericárdica, abordada por toracotomia ântero-lateral direita. Setenta por cento dos pacientes apresentaram ascite no pós-operatório. Seis pacientes morreram no primeiro mês pós-operatório, respectivamente pelas seguintes causas: choque séptico com ascite infectada, insuficiência renal, erro de técnica, insuficiência múltipla de órgäos com isquemia do miocárdio e dois por síndromes hepato-renal...