BackgroundPulmonary arterial hypertension (PAH) is a group of vascular diseases that produce right ventricular dysfunction, heart failure syndrome, and death. Although the majority of patients appear idiopathic, accumulated research work combined with current sequencing technology show that many gene variants could be an important component of the disease. However, current guidelines, clinical practices, and available gene panels focus the diagnosis of PAH on a relatively low number of genes and variants associated with the bone morphogenic proteins and transforming Growth Factor-β pathways, such as the BMPR2, ACVRL1, CAV1, ENG, and SMAD9.MethodsTo provide an expanded view of the genes and variants associated with PAH, we performed a systematic literature review. Facilitated by a web tool, we classified, curated, and annotated most of the genes and PubMed abstracts related to PAH, in which many of the mutations and variants were not annotated in public databases such as ClinVar from NCBI. The gene list generated was compared with other available tests.ResultsOur results reveal that there is genetic evidence for at least 30 genes, of which 21 genes shown specific mutations. Most of the genes are not covered by current available genetic panels. Many of these variants were not annotated in the ClinVar database and a mapping of these mutations suggest that next generation sequencing is needed to cover all mutations found in PAH or related diseases. A pathway analysis of these genes indicated that, in addition to the BMP and TGFβ pathways, there was connections with the nitric oxide, prostaglandin, and calcium homeostasis signalling, which may be important components in PAH.ConclusionOur systematic review proposes an expanded gene panel for more accurate characterization of the genetic incidence and risk in PAH. Their usage would increase the knowledge of PAH in terms of genetic counseling, early diagnosis, and potential prognosis of the disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-017-0440-5) contains supplementary material, which is available to authorized users.

Gastric cancer (GC) pathogenesis is complex and heterogeneous, reflecting morphological, molecular, and genetic diversity. Diffuse gastric cancer (DGC) and intestinal gastric cancer (IGC) are the major histological types. GC may be sporadic or hereditary; sporadic GC is related to environmental and genetic low-risk factors and hereditary GC is caused by inherited high-risk mutations, so far identified only for the diffuse histotype.DGC phenotypic heterogeneity challenges the current understanding of molecular mechanisms underlying carcinogenesis. The definition of a DGC-specific mutational profile remains controversial, possibly reflecting the heterogeneity of DGC-related histological subtypes (Signet-Ring Cell Carcinoma (SRCC) and Poorly Cohesive Carcinoma not otherwise specified (PCC-NOS)). Indeed, DGC and DGC-related subtypes may present specific mutational profiles underlying the particularly aggressive behaviour and dismal prognosis of DGC vs IGC and PCC-NOS vs SRCC.In this systematic review, we revised the histological presentations, molecular classifications, and approved therapies for gastric cancer, with a focus on DGC. We then analysed results from the most relevant studies, reporting mutational analysis data specifying mutational frequencies, and their relationship with DGC and IGC histological types, and with specific DGC subtypes (SRCC and PCC-NOS). We aimed at identifying histology-associated mutational profiles with an emphasis in DGC and its subtypes (DGC vs IGC; sporadic vs hereditary DGC; and SRCC vs PCC-NOS). We further used these mutational profiles to identify the most commonly affected molecular pathways and biological functions, and explored the clinical trials directed specifically to patients with DGC. This systematic analysis is expected to expose a DGC-specific molecular profile and shed light into potential targets for therapeutic intervention, which are currently missing.

Background and objectiveAnalysis, annotation and curation of biomedical scientific literature is a recurrent task in biomedical research, database curation and clinics. Commonly, the reading is centered on concepts such as genes, diseases or molecules. Database curators may also need to annotate published abstracts related to a specific topic. However, few free and intuitive tools exist to assist users in this context. Therefore, we developed PubTerm, a web tool to organize, categorize, curate and annotate a large number of PubMed abstracts related to biological entities such as genes, diseases, chemicals, species, sequence variants and other related information.MethodsA variety of interfaces were implemented to facilitate curation and annotation, including the organization of abstracts by terms, by the co-occurrence of terms or by specific phrases. Information includes statistics on the occurrence of terms. The abstracts, terms and other related information can be annotated and categorized using user-defined categories. The session information can be saved and restored, and the data can be exported to other formats.ResultsThe pipeline in PubTerm starts by specifying a PubMed query or list of PubMed identifiers. Then, the user can specify three lists of categories and specify what information will be highlighted in which colors. The user then utilizes the `term view’ to organize the abstracts by gene, disease, species or other information to facilitate the annotation and categorization of terms or abstracts. Other views also facilitate the exploration of abstracts and connections between terms. We have used PubTerm to quickly and efficiently curate collections of more than 400 abstracts that mention more than 350 genes to generate revised lists of susceptibility genes for diseases. An example is provided for pulmonary arterial hypertension.ConclusionsPubTerm saves time for literature revision by assisting with annotation organization and knowledge acquisition.

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