Meta-analysis reveals conserved cell cycle transcriptional network across multiple human cell types.

BMC Genomics. 2017 Jan 05;18(1):30

Authors: Giotti B, Joshi A, Freeman TC

Abstract
BACKGROUND: Cell division is central to the physiology and pathology of all eukaryotic organisms. The molecular machinery underpinning the cell cycle has been studied extensively in a number of species and core aspects of it have been found to be highly conserved. Similarly, the transcriptional changes associated with this pathway have been studied in different organisms and different cell types. In each case hundreds of genes have been reported to be regulated, however there seems to be little consensus in the genes identified across different studies. In a recent comparison of transcriptomic studies of the cell cycle in different human cell types, only 96 cell cycle genes were reported to be the same across all studies examined.
RESULTS: Here we perform a systematic re-examination of published human cell cycle expression data by using a network-based approach to identify groups of genes with a similar expression profile and therefore function. Two clusters in particular, containing 298 transcripts, showed patterns of expression consistent with cell cycle occurrence across the four human cell types assessed.
CONCLUSIONS: Our analysis shows that there is a far greater conservation of cell cycle-associated gene expression across human cell types than reported previously, which can be separated into two distinct transcriptional networks associated with the G1/S-S and G2-M phases of the cell cycle. This work also highlights the benefits of performing a re-analysis on combined datasets.

PMID: 28056781 [PubMed - in process]

Predicting High-Impact Pharmacological Targets by Integrating Transcriptome and Text-Mining Features.

J Pharm Pharm Sci. 2016 Oct - Dec;19(4):475-495

Authors: Mayburd A, Baranova A

Abstract
PURPOSE: Novel, "outside of the box" approaches are needed for evaluating candidate molecules, especially in oncology. Throughout the years of 2000-2010, the efficiency of drug development fell to barely acceptable levels, and in the second decade of this century, levels have improved only marginally. This dismal condition continues despite unprecedented progress in the development of a variety of high-throughput tools, computational methods, aggregated databases, drug repurposing programs and innovative chemistries. Here we tested a hypothesis that the economic impact of targeting a particular gene product is predictable a priori by employing a combination of transcriptome profiles and quantitative metrics reflecting existing literature.
METHODS: To extract classification features, the gene expression patterns of a posteriori high-impact and low-impact anti-cancer target sets were compared. To minimize the possible bias of text-mining, the number of manuscripts published prior to the first clinical trial or relevant review paper, as well as its first derivative in this interval, were collected and used as quantitative metrics of public interest.
RESULTS: By combining the gene expression and literature mining features, a 4-fold enrichment in high-impact targets was produced, resulting in a favourable ROC curve analysis for the top impact targets. The dataset was enriched by the highest impact anti-cancer targets, while demonstrating drastic differences in economic value between high and low-impact targets. Known anti-cancer products of EGFR, ERBB2, CYP19A1/aromatase, MTOR, PTGS2, tubulin, VEGFA, BRAF, PGR, PDGFRA, SRC, REN, CSF1R, CTLA4 and HSP90AA1 genes received the highest scores for predicted impact, while microsomal steroid sulfatase, anticoagulant protein C, p53, CDKN2A, c-Jun, and TNSFS11 were highlighted as most promising research-stage targets.
CONCLUSIONS: A significant cost reduction may be achieved by a priori impact assessment of targets and ligands before their development or repurposing. Expanding a suite of combinational treatments could also decrease the costs, while achieving a higher impact per developed ligand. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

PMID: 28057171 [PubMed - in process]

Cadherin 26 is an alpha integrin-binding epithelial receptor regulated during allergic inflammation.

Mucosal Immunol. 2017 Jan 04;:

Authors: Caldwell JM, Collins MH, Kemme KA, Sherrill JD, Wen T, Rochman M, Stucke EM, Amin L, Tai H, Putnam PE, Jiménez-Dalmaroni MJ, Wormald MR, Porollo A, Abonia JP, Rothenberg ME

Abstract
Cadherins (CDH) mediate diverse processes critical in inflammation, including cell adhesion, migration, and differentiation. Herein, we report that the uncharacterized cadherin 26 (CDH26) is highly expressed by epithelial cells in human allergic gastrointestinal tissue. In vitro, CDH26 promotes calcium-dependent cellular adhesion of cells lacking endogenous CDHs by a mechanism involving homotypic binding and interaction with catenin family members (alpha, beta, and p120), as assessed by biochemical assays. Additionally, CDH26 enhances cellular adhesion to recombinant integrin α4β7 in vitro; conversely, recombinant CDH26 binds αE and α4 integrins in biochemical and cellular functional assays, respectively. Interestingly, CDH26-Fc inhibits activation of human CD4(+) T cells in vitro including secretion of IL-2. Taken together, we have identified a novel functional CDH regulated during allergic responses with unique immunomodulatory properties, as it binds α4 and αE integrins and regulates leukocyte adhesion and activation, and may thus represent a novel checkpoint for immune regulation and therapy via CDH26-Fc.Mucosal Immunology advance online publication 4 January 2017. doi:10.1038/mi.2016.120.

PMID: 28051089 [PubMed - as supplied by publisher]

Identifying New Antiepileptic Drugs Through Genomics-Based Drug Repurposing.

Hum Mol Genet. 2017 Jan 04;:

Authors: Mirza N, Sills GJ, Pirmohamed M, Marson AG

Abstract
Currently available antiepileptic drugs (AEDs) fail to control seizures in 30% of patients. Genomics-based drug repurposing (GBR) offers the potential of savings in the time and cost of developing new AEDs. In the current study, we used published data and software to identify the transcriptomic signature of chornic temporal lobe epilepsy and the drugs that reverse it. After filtering out compounds based on exclusion criteria, such as toxicity, 36 drugs were retained. 11 of the 36 drugs identified (>30%) have published evidence of antiepileptic efficacy (for example, curcumin) or antiepileptogenic affect (for example, atorvastatin) in recognised rodent models or patients. By objectively annotating all ∼20,000 compounds in the LINCS database as either having published evidence of antiepileptic efficacy or lacking such evidence, we demonstrated that our set of repurposable drugs is ∼6-fold more enriched with drugs having published evidence of antiepileptic efficacy in animal models than expected by chance (p-value <0.006). Further, we showed that another of our GBR-identified drugs, the commonly-used well-tolerated antihyperglycemic sitagliptin, produces a dose-dependent reduction in seizures in a mouse model of pharmacoresistant epilepsy. In conclusion, GBR successfully identifies compounds with antiepileptic efficacy in animal models and, hence, it is an appealing methodology for the discovery of potential AEDs.

PMID: 28053048 [PubMed - as supplied by publisher]

Mouse Models for Drug Discovery. Can New Tools and Technology Improve Translational Power?

ILAR J. 2016 Dec;57(2):178-185

Authors: Zuberi A, Lutz C

Abstract
The use of mouse models in biomedical research and preclinical drug evaluation is on the rise. The advent of new molecular genome-altering technologies such as CRISPR/Cas9 allows for genetic mutations to be introduced into the germ line of a mouse faster and less expensively than previous methods. In addition, the rapid progress in the development and use of somatic transgenesis using viral vectors, as well as manipulations of gene expression with siRNAs and antisense oligonucleotides, allow for even greater exploration into genomics and systems biology. These technological advances come at a time when cost reductions in genome sequencing have led to the identification of pathogenic mutations in patient populations, providing unprecedented opportunities in the use of mice to model human disease. The ease of genetic engineering in mice also offers a potential paradigm shift in resource sharing and the speed by which models are made available in the public domain. Predictively, the knowledge alone that a model can be quickly remade will provide relief to resources encumbered by licensing and Material Transfer Agreements. For decades, mouse strains have provided an exquisite experimental tool to study the pathophysiology of the disease and assess therapeutic options in a genetically defined system. However, a major limitation of the mouse has been the limited genetic diversity associated with common laboratory mice. This has been overcome with the recent development of the Collaborative Cross and Diversity Outbred mice. These strains provide new tools capable of replicating genetic diversity to that approaching the diversity found in human populations. The Collaborative Cross and Diversity Outbred strains thus provide a means to observe and characterize toxicity or efficacy of new therapeutic drugs for a given population. The combination of traditional and contemporary mouse genome editing tools, along with the addition of genetic diversity in new modeling systems, are synergistic and serve to make the mouse a better model for biomedical research, enhancing the potential for preclinical drug discovery and personalized medicine.

PMID: 28053071 [PubMed - in process]

Familial florid osseous dysplasia: a report with review of the literature.

BMJ Case Rep. 2016 Mar 30;2016:

Authors: Kucukkurt S, Rzayev S, Baris E, Atac MS

Abstract
There are three types of osseous dysplasia: periapical cemental dysplasia (PCD), focal cemento-osseous dysplasia (FCD) and florid osseous dysplasia (FOD). While PCD is often observed in mandibular anterior teeth, FCD mainly affects mandibular posterior teeth. FOD, on the other hand, commonly involves both jaws. FOD is a type of sclerosing disease that is characterised by intense opaque masses and many areas with different densities. Genetic heritance of FOD is unusual, with only a few reported cases. We describe a case of FOD that affected three family members, discuss its clinical, radiological and histological characteristics, and review the literature.

PMID: 27030456 [PubMed - indexed for MEDLINE]

IgG4-related mastitis, a rare disease, can radiologically and histologically mimic malignancy.

BMJ Case Rep. 2016 Mar 23;2016:

Authors: Yamada R, Horiguchi S, Yamashita T, Kamisawa T

Abstract
IgG4-related disease (IgG4-RD) is characterised by high serum concentrations of IgG4, dense lymphoplasmacytic infiltrates, storiform fibrosis and increased IgG4-positive plasma cells in tissues. This systemic disease occurs in various organs metachronously, but IgG4-related mastitis appears extremely rare. We report a case of IgG4-related mastitis, radiologically considered to represent breast cancer mainly composed of intraductal component and requiring histological differentiation from mucosa-associated lymphoid tissue (MALT) lymphoma. The breast mass disappeared with steroid therapy. When patients have a breast mass, regardless of the presence or absence of IgG4-RD, IgG4-related mastitis should be considered in addition to breast cancer. If histological findings show dense lymphoplasmacytic infiltrates, IgG4-related mastitis should be suspected in addition to malignant lymphoma, and lack of monoclonality should be confirmed. To avoid unnecessary surgery or chemotherapy, knowledge and accurate diagnosis of the entity of IgG4-related mastitis is necessary.

PMID: 27009197 [PubMed - indexed for MEDLINE]

B-cell lymphoma of the heart: A rare diagnosis.

Rev Port Cardiol. 2014 Dec;33(12):803.e1-3

Authors: Matos AP, Palas J, Doulaptsis C, Ramalho M, Duarte S, Bogaert J

Abstract
We present a case of a primary cardiac lymphoma in a 60-year-old woman. The clinical presentation was non-specific and the diagnosis was suggested by its appearance on multidetector computed tomography. The final diagnosis was achieved by histopathological study and was corroborated by a decrease in tumor volume after targeted chemotherapy. A brief review of the appearance of primary cardiac lymphomas in imaging studies is presented.

PMID: 25459635 [PubMed - indexed for MEDLINE]

Ontology construction and application in practice case study of health tourism in Thailand.

Springerplus. 2016;5(1):2106

Authors: Chantrapornchai C, Choksuchat C

Abstract
Ontology is one of the key components in semantic webs. It contains the core knowledge for an effective search. However, building ontology requires the carefully-collected knowledge which is very domain-sensitive. In this work, we present the practice of ontology construction for a case study of health tourism in Thailand. The whole process follows the METHONTOLOGY approach, which consists of phases: information gathering, corpus study, ontology engineering, evaluation, publishing, and the application construction. Different sources of data such as structure web documents like HTML and other documents are acquired in the information gathering process. The tourism corpora from various tourism texts and standards are explored. The ontology is evaluated in two aspects: automatic reasoning using Pellet, and RacerPro, and the questionnaires, used to evaluate by experts of the domains: tourism domain experts and ontology experts. The ontology usability is demonstrated via the semantic web application and via example axioms. The developed ontology is actually the first health tourism ontology in Thailand with the published application.

PMID: 28053835 [PubMed - in process]

RegenBase: a knowledge base of spinal cord injury biology for translational research.

Database (Oxford). 2016;2016:

Authors: Callahan A, Abeyruwan SW, Al-Ali H, Sakurai K, Ferguson AR, Popovich PG, Shah NH, Visser U, Bixby JL, Lemmon VP

Abstract
Spinal cord injury (SCI) research is a data-rich field that aims to identify the biological mechanisms resulting in loss of function and mobility after SCI, as well as develop therapies that promote recovery after injury. SCI experimental methods, data and domain knowledge are locked in the largely unstructured text of scientific publications, making large scale integration with existing bioinformatics resources and subsequent analysis infeasible. The lack of standard reporting for experiment variables and results also makes experiment replicability a significant challenge. To address these challenges, we have developed RegenBase, a knowledge base of SCI biology. RegenBase integrates curated literature-sourced facts and experimental details, raw assay data profiling the effect of compounds on enzyme activity and cell growth, and structured SCI domain knowledge in the form of the first ontology for SCI, using Semantic Web representation languages and frameworks. RegenBase uses consistent identifier schemes and data representations that enable automated linking among RegenBase statements and also to other biological databases and electronic resources. By querying RegenBase, we have identified novel biological hypotheses linking the effects of perturbagens to observed behavioral outcomes after SCI. RegenBase is publicly available for browsing, querying and download.Database URL:http://regenbase.org.

PMID: 27055827 [PubMed - indexed for MEDLINE]

Participant-perceived understanding and perspectives on pharmacogenomics: the Mayo Clinic RIGHT protocol (Right Drug, Right Dose, Right Time).

Genet Med. 2017 Jan 05;:

Authors: Olson JE, Rohrer Vitek CR, Bell EJ, McGree ME, Jacobson DJ, St Sauver JL, Caraballo PJ, Griffin JM, Roger VL, Bielinski SJ

Abstract
PURPOSE: To examine predictors of understanding preemptive CYP2D6 pharmacogenomics test results and to identify key features required to improve future educational efforts of preemptive pharmacogenomics testing.
METHODS: One thousand ten participants were surveyed after receiving preemptive CYP2D6 pharmacogenomics test results.
RESULTS: Eighty-six percent (n = 869) of patients responded. Of the responders, 98% were white and 55% were female; 57% had 4 years or more of post-secondary education and an average age of 58.9 ± 5.5 years. Twenty-six percent said that they only somewhat understood their results and 7% reported they did not understand them at all. Only education predicted understanding. The most common suggestion for improvement was the use of layperson's terms when reporting results. In addition, responders suggested that results should be personalized by referring to medications that they were currently using. Of those reporting imperfect drug adherence, most (91%) reported they would be more likely to use medication as prescribed if pharmacogenomic information was used to help select the drug or dose.
CONCLUSION: Despite great efforts to simplify pharmacogenomic results (or because of them), approximately one-third of responders did not understand their results. Future efforts need to provide more examples and tailor results to the individual. Incorporation of pharmacogenomics is likely to improve medication adherence.Genet Med advance online publication 05 January 2017Genetics in Medicine (2017); doi:10.1038/gim.2016.192.

PMID: 28055020 [PubMed - as supplied by publisher]

CFTR structure: lassoing cystic fibrosis.

Nat Struct Mol Biol. 2017 Jan 05;24(1):13-14

Authors: Ford B

PMID: 28054564 [PubMed - in process]

Two cases of non-cystic fibrosis (CF) bronchiectasis with allergic bronchopulmonary aspergillosis.

Respir Med Case Rep. 2017;20:68-71

Authors: De H, Azad SM, Giri PP, Pal P, Ghosh A, Maitra A

Abstract
Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction in patients with asthma or cystic fibrosis (CF), which is associated with bronchi colonized by the fungus Aspergillus species, most often Aspergillus fumigatus. ABPA is an important consideration for asthmatics that do not respond to asthma management or with recurrent chest infections and deteriorating lung function in children with cystic fibrosis. We present two cases of non CF bronchiectasis associated with ABPA who presented to our hospital with recurrent hospitalisations of undiagnosed aetiology.

PMID: 28053855 [PubMed - in process]

The international primary ciliary dyskinesia cohort (iPCD Cohort): methods and first results.

Eur Respir J. 2017 Jan;49(1):

Authors: Goutaki M, Maurer E, Halbeisen FS, Amirav I, Barbato A, Behan L, Boon M, Casaulta C, Clement A, Crowley S, Haarman E, Hogg C, Karadag B, Koerner-Rettberg C, Leigh MW, Loebinger MR, Mazurek H, Morgan L, Nielsen KG, Omran H, Schwerk N, Scigliano S, Werner C, Yiallouros P, Zivkovic Z, Lucas JS, Kuehni CE, PCD Italian Consortium, Swiss PCD Group, French Reference Centre for Rare Lung Diseases, Genetic Disorders of Mucociliary Clearance Consortium

Abstract
Data on primary ciliary dyskinesia (PCD) epidemiology is scarce and published studies are characterised by low numbers. In the framework of the European Union project BESTCILIA we aimed to combine all available datasets in a retrospective international PCD cohort (iPCD Cohort).We identified eligible datasets by performing a systematic review of published studies containing clinical information on PCD, and by contacting members of past and current European Respiratory Society Task Forces on PCD. We compared the contents of the datasets, clarified definitions and pooled them in a standardised format.As of April 2016 the iPCD Cohort includes data on 3013 patients from 18 countries. It includes data on diagnostic evaluations, symptoms, lung function, growth and treatments. Longitudinal data are currently available for 542 patients. The extent of clinical details per patient varies between centres. More than 50% of patients have a definite PCD diagnosis based on recent guidelines. Children aged 10-19 years are the largest age group, followed by younger children (≤9 years) and young adults (20-29 years).This is the largest observational PCD dataset available to date. It will allow us to answer pertinent questions on clinical phenotype, disease severity, prognosis and effect of treatments, and to investigate genotype-phenotype correlations.

PMID: 28052956 [PubMed - in process]

Hypoxia and sterile inflammation in cystic fibrosis airways: mechanisms and potential therapies.

Eur Respir J. 2017 Jan;49(1):

Authors: Montgomery ST, Mall MA, Kicic A, Stick SM, AREST CF

Abstract
Cystic fibrosis is one of the most common autosomal recessive genetic diseases in Caucasian populations. Diagnosis via newborn screening and targeted nutritional and antibiotic therapy have improved outcomes, however respiratory failure remains the key cause of morbidity and mortality. Progressive respiratory disease in cystic fibrosis is characterised by chronic neutrophilic airway inflammation associated with structural airway damage leading to bronchiectasis and decreased lung function. Mucus obstruction is a characteristic early abnormality in the cystic fibrosis airway, associated with neutrophilic inflammation often in the absence of detectable infection. Recent studies have suggested a link between hypoxic cell death and sterile neutrophilic inflammation in cystic fibrosis and other diseases via the IL-1 signalling pathway. In this review, we consider recent evidence regarding the cellular responses to respiratory hypoxia as a potential driver of sterile neutrophilic inflammation in the lung, current knowledge on hypoxia as a pathogenic mechanism in cystic fibrosis and the potential for current and future therapies to alleviate hypoxia-driven sterile inflammation.

PMID: 28052955 [PubMed - in process]

Lung Allocation Score: A Single-Center Simulation.

Transplant Proc. 2016 Mar;48(2):391-4

Authors: Rosso L, Palleschi A, Tosi D, Mendogni P, Righi I, Carrinola R, Montoli M, Damarco F, Rossetti V, Morlacchi LC, Nosotti M

Abstract
BACKGROUND: The lung allocation score (LAS) was introduced in the United States in May 2005 with the main goal of reducing the waiting list mortality of patients with end-stage lung diseases, but also to enhance the lung transplant benefit and improve the management of urgent candidates. Several papers have reported that LAS resulted in a reduction of the waiting list mortality but no significant survival benefit was noted.
METHODS: We evaluate the usefulness of LAS as a predictor for lung transplantation outcome in 123 patients listed for lung transplantation in an Italian center. Primary endpoints were waiting list mortality and posttransplant mortality at 1 year; secondary endpoints included perioperative circulatory support, cardiopulmonary bypass, primary graft dysfunction, and long-term survival after transplantation.
RESULTS: We observed the absence of correlation between LAS and waiting list mortality. The LAS did not affect the long-term survival in our population.
CONCLUSIONS: High LAS was predictive of primary graft dysfunction of grade 3 in the first 72 hours after transplantation.

PMID: 27109963 [PubMed - indexed for MEDLINE]

Mouse Models for Drug Discovery. Can New Tools and Technology Improve Translational Power?

ILAR J. 2016 Dec;57(2):178-185

Authors: Zuberi A, Lutz C

Abstract
The use of mouse models in biomedical research and preclinical drug evaluation is on the rise. The advent of new molecular genome-altering technologies such as CRISPR/Cas9 allows for genetic mutations to be introduced into the germ line of a mouse faster and less expensively than previous methods. In addition, the rapid progress in the development and use of somatic transgenesis using viral vectors, as well as manipulations of gene expression with siRNAs and antisense oligonucleotides, allow for even greater exploration into genomics and systems biology. These technological advances come at a time when cost reductions in genome sequencing have led to the identification of pathogenic mutations in patient populations, providing unprecedented opportunities in the use of mice to model human disease. The ease of genetic engineering in mice also offers a potential paradigm shift in resource sharing and the speed by which models are made available in the public domain. Predictively, the knowledge alone that a model can be quickly remade will provide relief to resources encumbered by licensing and Material Transfer Agreements. For decades, mouse strains have provided an exquisite experimental tool to study the pathophysiology of the disease and assess therapeutic options in a genetically defined system. However, a major limitation of the mouse has been the limited genetic diversity associated with common laboratory mice. This has been overcome with the recent development of the Collaborative Cross and Diversity Outbred mice. These strains provide new tools capable of replicating genetic diversity to that approaching the diversity found in human populations. The Collaborative Cross and Diversity Outbred strains thus provide a means to observe and characterize toxicity or efficacy of new therapeutic drugs for a given population. The combination of traditional and contemporary mouse genome editing tools, along with the addition of genetic diversity in new modeling systems, are synergistic and serve to make the mouse a better model for biomedical research, enhancing the potential for preclinical drug discovery and personalized medicine.

PMID: 28053071 [PubMed - in process]

Prevention of Evisceration or Enucleation in Endogenous Bacterial Panophthalmitis with No Light Perception and Scleral Abscess.

PLoS One. 2017;12(1):e0169603

Authors: Chen KJ, Chen YP, Chao AN, Wang NK, Wu WC, Lai CC, Chen TL

Abstract
Panophthalmitis is the most extensive ocular involvement in endophthalmitis with inflammation in periocular tissues. Severe inflammation of the anterior and posterior segments is frequently accompanied by corneal opacity, scleral abscess, and perforation or rupture. Enucleation or evisceration was the only remaining viable treatment option when all options to salvage the eye had been exhausted. The purpose of this retrospective study is to examine the outcomes of patients with endogenous bacterial panophthalmitis, no light perception and scleral abscess who were treated with multiple intravitreal and periocular injections of antibiotics and dexamethasone. Evaluation included spreading of infection to contiguous or remote sites, following evisceration or enucleation, and sympathetic ophthalmia. Eighteen patients were diagnosed with EBP, with liver abscesses in eight patients, retroperitoneal infection in four, pneumonia in two, infective endocarditis in one, cellulitis in one, drug abuse in one, and mycotic pseudoaneurysm in one. Culture results were positive for Klebsiella pneumoniae in 12 patients, Streptococcus spp. in three, Pseudomonas aeruginosa in one, Escherichia coli in one, and Staphylococcus aureus in one. The average number of periocular injections was 2.2, and the average number of intravitreal injections was 5.8. No eye required evisceration or enucleation and developed the spreading of infection to contiguous or remote sites during the follow-up. No sympathetic ophthalmia was observed in the fellow eye of all patients. Prevention of evisceration or enucleation in patients with EBP, NLP and scleral abscess can be achieved by multiple intravitreal and periocular injections of antibiotics and dexamethasone.

PMID: 28056067 [PubMed - in process]

An analysis of disease-gene relationship from Medline abstracts by DigSee.

Sci Rep. 2017 Jan 05;7:40154

Authors: Kim J, Kim JJ, Lee H

Abstract
Diseases are developed by abnormal behavior of genes in biological events such as gene regulation, mutation, phosphorylation, and epigenetics and post-translational modification. Many studies of text mining attempted to identify the relationship between gene and disease by mining the literature, but they did not consider the biological events in which genes show abnormal behaviour in response to diseases. In this study, we propose to identify disease-related genes that are involved in the development of disease through biological events from Medline abstracts. We identified associations between 13,054 genes and 4,494 disease types, which cover more disease-related genes than manually curated databases for all disease types (e.g., Online Mendelian Inheritance in Man) and also than those for specific diseases (e.g., Alzheimer's disease and hypertension). We show that the text mining findings are reliable, as per the PubMed scale, in that the disease-disease relationships inferred from the literature-wide findings are similar to those inferred from manually curated databases in a well-known study. In addition, literature-wide distribution of biological events across disease types reveals different characteristics of disease types.

PMID: 28054646 [PubMed - in process]

BRONCO: Biomedical entity Relation ONcology COrpus for extracting gene-variant-disease-drug relations.

Database (Oxford). 2016;2016:

Authors: Lee K, Lee S, Park S, Kim S, Kim S, Choi K, Tan AC, Kang J

Abstract
Comprehensive knowledge of genomic variants in a biological context is key for precision medicine. As next-generation sequencing technologies improve, the amount of literature containing genomic variant data, such as new functions or related phenotypes, rapidly increases. Because numerous articles are published every day, it is almost impossible to manually curate all the variant information from the literature. Many researchers focus on creating an improved automated biomedical natural language processing (BioNLP) method that extracts useful variants and their functional information from the literature. However, there is no gold-standard data set that contains texts annotated with variants and their related functions. To overcome these limitations, we introduce a Biomedical entity Relation ONcology COrpus (BRONCO) that contains more than 400 variants and their relations with genes, diseases, drugs and cell lines in the context of cancer and anti-tumor drug screening research. The variants and their relations were manually extracted from 108 full-text articles. BRONCO can be utilized to evaluate and train new methods used for extracting biomedical entity relations from full-text publications, and thus be a valuable resource to the biomedical text mining research community. Using BRONCO, we quantitatively and qualitatively evaluated the performance of three state-of-the-art BioNLP methods. We also identified their shortcomings, and suggested remedies for each method. We implemented post-processing modules for the three BioNLP methods, which improved their performance.Database URL:http://infos.korea.ac.kr/bronco.

PMID: 27074804 [PubMed - indexed for MEDLINE]