Splicing Express: a software suite for alternative splicing analysis using next-generation sequencing data.

Motivation. Alternative splicing events (ASEs) are prevalent in the transcriptome of eukaryotic species and are known to influence many biological phenomena. The identification and quantification of these events are crucial for a better understanding of biological processes. Next-generation DNA sequencing technologies have allowed deep characterization of transcriptomes and made it possible to address these issues. ASEs analysis, however, represents a challenging task especially when many different samples need to be compared. Some popular tools for the analysis of ASEs are known to report thousands of events without annotations and/or graphical representations. A new tool for the identification and visualization of ASEs is here described, which can be used by biologists without a solid bioinformatics background. Results. A software suite named Splicing Express was created to perform ASEs analysis from transcriptome sequencing data derived from next-generation DNA sequencing platforms. Its major goal is to serve the needs of biomedical researchers who do not have bioinformatics skills. Splicing Express performs automatic annotation of transcriptome data (GTF files) using gene coordinates available from the UCSC genome browser and allows the analysis of data from all available species. The identification of ASEs is done by a known algorithm previously implemented in another tool named Splooce. As a final result, Splicing Express creates a set of HTML files composed of graphics and tables designed to describe the expression profile of ASEs among all analyzed samples. By using RNA-Seq data from the Illumina Human Body Map and the Rat Body Map, we show that Splicing Express is able to perform all tasks in a straightforward way, identifying well-known specific events. Availability and Implementation. Splicing Express is written in Perl and is suitable to run only in UNIX-like systems. More details can be found at: http://www.bioinformatics-brazil.org/splicingexpress.

SPLOOCE: a new portal for the analysis of human splicing variants.

Understanding alternative splicing is crucial to elucidate the mechanisms behind several biological phenomena, including diseases. The huge amount of expressed sequences available nowadays represents an opportunity and a challenge to catalog and display alternative splicing events (ASEs). Although several groups have faced this challenge with relative success, we still lack a computational tool that uses a simple and straightforward method to retrieve, name and present ASEs. Here we present SPLOOCE, a portal for the analysis of human splicing variants. SPLOOCE uses a method based on regular expressions for retrieval of ASEs. We propose a simple syntax that is able to capture the complexity of ASEs.

SurfaceomeDB: a cancer-orientated database for genes encoding cell surface proteins.

Cell surface proteins (CSPs) are excellent targets for the development of diagnostic and therapeutic reagents, and it is estimated that 10-20% of all genes in the human genome encode CSPs. In an effort to integrate all data publicly available for genes encoding cell surface proteins, a database (SurfaceomeDB) was developed. SurfaceomeDB is a gene-centered portal containing different types of information, including annotation for gene expression, protein domains, somatic mutations in cancer, and protein-protein interactions for all human genes encoding CSPs. SurfaceomeDB was implemented as an integrative and relational database in a user-friendly web interface, where users can search for gene name, gene annotation, or keywords. There is also a streamlined graphical representation of all data provided and links to the most important data repositories and databases, such as NCBI, UCSC Genome Browser, and EBI.

Distinct patterns of somatic alterations in a lymphoblastoid and a tumor genome derived from the same individual.

Although patterns of somatic alterations have been reported for tumor genomes, little is known on how they compare with alterations present in non-tumor genomes. A comparison of the two would be crucial to better characterize the genetic alterations driving tumorigenesis. We sequenced the genomes of a lymphoblastoid (HCC1954BL) and a breast tumor (HCC1954) cell line derived from the same patient and compared the somatic alterations present in both. The lymphoblastoid genome presents a comparable number and similar spectrum of nucleotide substitutions to that found in the tumor genome. However, a significant difference in the ratio of non-synonymous to synonymous substitutions was observed between both genomes (P = 0.031). Protein-protein interaction analysis revealed that mutations in the tumor genome preferentially affect hub-genes (P = 0.0017) and are co-selected to present synergistic functions (P < 0.0001). KEGG analysis showed that in the tumor genome most mutated genes were organized into signaling pathways related to tumorigenesis. No such organization or synergy was observed in the lymphoblastoid genome. Our results indicate that endogenous mutagens and replication errors can generate the overall number of mutations required to drive tumorigenesis and that it is the combination rather than the frequency of mutations that is crucial to complete tumorigenic transformation.

Modeling cancer: integration of "omics" information in dynamic systems.

The last 10 years have seen the rise of many technologies that produce an unprecedented amount of genome-scale data from many organisms. Although the research community has been successful in exploring these data, many challenges still persist. One of them is the effective integration of such data sets directly into approaches based on mathematical modeling of biological systems. Applications in cancer are a good example. The bridge between information and modeling in cancer can be achieved by two major types of complementary strategies. First, there is a bottom-up approach, in which data generates information about structure and relationship between components of a given system. In addition, there is a top-down approach, where cybernetic and systems-theoretical knowledge are used to create models that describe mechanisms and dynamics of the system. These approaches can also be linked to yield multi-scale models combining detailed mechanism and wide biological scope. Here we give an overall picture of this field and discuss possible strategies to approach the major challenges ahead.

Automatic correspondence of tags and genes (ACTG): a tool for the analysis of SAGE, MPSS and SBS data.

UNLABELLED: A critical step in any SAGE, MPSS and SBS data analysis is tag-to-gene assignment. Current available tools are limited by a tag-by-tag annotation process and/or do not provide the dataset that is used to produce a complete tag-to-gene mapping. We developed ACTG, a web-based application that allows a large-scale tag-to-gene mapping using several reference datasets. ACTG can annotate SAGE (14 or 21 bp), MPSS (17 or 20 bp) and SBS (16 bp) data for both human and mouse organisms. AVAILABILITY: http://retina.med.harvard.edu/ACTG/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A certificate program in health informatics: Brazil/USA experience.

Considering the continued demand for a large number of trained professionals we decided to offer a certificate program in health informatics. The objective is to prepare professionals to conduct research and implement the curriculum content in their original institutions. We selected 14 candidates from several national institutes. The disciplines are taught by Brazilian and US faculty. Researches conducted by the certificate students were relevant to Brazil's health needs. The goal is to promote better health informatics education, regardless of geographic distribution of students.

Training health informatics professionals in Brazil: rationale for the development of a new certificate program.

Current graduate degree programs in Brazil cannot fulfill the demand for highly trained health informatics practitioners. We have developed an intensive six-month program to train 20 students per year. They will receive partial subsidy from our bilateral training program and receive the title of Specialist in Health Informatics. They will benefit from a curriculum involving coursework and collaborative research designed by Brazilian and US-based faculty.

International training in health informatics: a Brazilian experience.

Technology is transforming not only the practice of health-care but also professional training and educational models. Developing countries, such as Brazil, are increasingly suffering from a severe shortage of health informatics specialists. Training of professionals in this field is expensive, and there is a limited supply of high-quality teaching resources available. We envision that training in health informatics can be better achieved if cultural and technological barriers are anticipated and the training program is prepared accordingly. We describe our four-year experience of a Brazil/USA training program and discuss lessons learned during its implementation. Eleven onsite courses, one seminar, and two conferences were developed under this unique initiative, which made possible the collaboration among different countries and distinguished leaders in the field of medical informatics.

Training in health informatics in Brazil.

Developing countries, such as Brazil, are increasingly suffering from a severe shortage of health informatics specialists. Training of professionals in this field is expensive, and there is a limited supply of high-quality teaching resources available. We report on five initiatives of the Brazil/USA training program in health informatics. The main goal of this program is to train professionals in establishing medical informatics programs in Brazilian universities and major healthcare facilities.