Sctensor detects many-to-many cell-cell interactions from single cell RNA-sequencing data.

BACKGROUND: Complex biological systems are described as a multitude of cell-cell interactions (CCIs). Recent single-cell RNA-sequencing studies focus on CCIs based on ligand-receptor (L-R) gene co-expression but the analytical methods are not appropriate to detect many-to-many CCIs. RESULTS: In this work, we propose scTensor, a novel method for extracting representative triadic relationships (or hypergraphs), which include ligand-expression, receptor-expression, and related L-R pairs. CONCLUSIONS: Through extensive studies with simulated and empirical datasets, we have shown that scTensor can detect some hypergraphs that cannot be detected using conventional CCI detection methods, especially when they include many-to-many relationships. scTensor is implemented as a freely available R/Bioconductor package.

Differences between patients with inpatient-onset and outpatient-onset acute lower gastrointestinal bleeding: An observational study.

BACKGROUND AND AIM: The clinical severity and course of acute lower gastrointestinal bleeding (ALGIB) are believed to differ between inpatient-onset and outpatient-onset cases, but no reports have investigated these issues in detail. We aimed to evaluate the clinical differences between inpatient-onset and outpatient-onset ALGIB. METHODS: Medical records of patients who had undergone emergency colonoscopy for ALGIB were retrospectively reviewed. The severity was evaluated using the NOBLADS score. Patients with obvious ALGIB relapse and/or persistent iron-deficiency anemia after emergency colonoscopy were considered to exhibit a poor clinical course. RESULTS: We reviewed 723 patients with ALGIB and divided them into the inpatient-onset cohort (172 patients) and outpatient-onset cohort (551 patients). Compared with the outpatient-onset cohort, the inpatient-onset cohort had a significantly higher proportion of patients with a poor clinical course (51.2% vs 21.6%; P < 0.001) and a significantly higher mean NOBLADS score (3.6 ± 1.1 vs 2.5 ± 1.0; P < 0.001). The most common bleeding source was acute hemorrhagic rectal ulcer (52.3%) in the inpatient-onset cohort and colonic diverticular bleeding (29.4%) in the outpatient-onset cohort. Multivariate analysis showed that a platelet count < 15 × 104 /µL and albumin concentration < 3 g/dL were significantly associated with a poor clinical course in the inpatient-onset cohort. CONCLUSIONS: The clinical course was significantly worse in the inpatient-onset cohort than in the outpatient-onset cohort. The bleeding source, clinical characteristics, and clinical course differed between the inpatient-onset and outpatient-onset cohorts. The clinical course in the inpatient-onset cohort may depend on the patient's condition at ALGIB onset.

Molecular biomarker identification for esophageal adenocarcinoma using endoscopic brushing and magnified endoscopy.

BACKGROUND: Barrett's esophagus (BE) is a predisposing factor for esophageal adenocarcinoma (EAC); however, the precise mechanism underlying this association remains unclear. The identification of biomarkers that are associated with an increased risk of BE progression to EAC would facilitate diagnosis and early treatment. Toward this goal, we aimed to identify biomarkers associated with BE and EAC in patients. METHODS: In conjunction with high-resolution magnified endoscopy with narrow-band imaging (ME-NBI), we obtained brushing samples from the long-segment BE (LSBE) or short-segment BE (SSBE) of patients with EAC or without EAC (control). To identify candidate biomarker genes, microarray analysis was performed for a training set of 28 American samples. To confirm the microarray results, expression levels of the 16 candidate biomarkers were evaluated by real-time polymerase chain reaction analysis, using samples collected from an additional 53 American patients. In addition, we also performed a functional analysis for these genes using Gene Ontology (GO) enrichment analysis. RESULTS: Among the 16 genes identified as differentially expressed by microarray analysis, the GO analysis indicated matrix metalloproteinase (MMP) family associated with 'collagen metabolic process' and 'multicellular organismal macromolecule metabolic process' as the two top biological processes. Brushing samples of patients with EAC showed up-regulated expression of decay-accelerating factors (DAF and CD55) and topoisomerase type Iiα (TOP2A), and down-regulated expression of the sodium channel epithelial 1 beta subunit (SCNN1B). CONCLUSIONS: The up-regulation of CD55 and TOP2A, and the down-regulation of SCNN1B were common to the brushing samples and might serve as molecular biomarkers for identifying EAC in patients with SSBE. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) (000004004).

Analysis of the colonic mucosa associated microbiota (MAM) using brushing samples during colonic endoscopic procedures.

The mucosa-associated microbiota is an important component in human microbiota. The aim was to investigate mucosa-associated microbiota using brush samples during endoscopic procedures and compare with fecal microbiota. Seven patients who were planning to undergo a routine colonoscopy were recruited. Mucosal brushing samples were taken from 3 sites (terminal ileum, ascending and sigmoid colon), and a fecal sample was taken on the morning of colonoscopy. The samples were immediately placed in microcentrifuge tubes containing DNA stabilization reagent and analyzed using the next generation sequencer. The individual differences in microbiota were more evident than the differences of the sampling sites. Actinobacteria was more abundant and Bacteroidetes was less in the brush samples than those in the fecal samples. Taxonomic composition at the genus level and the proportion of genes responsible for some functions in the brushing samples tended to be different from those in the fecal samples. Bulleidia and Oribacteriumi were significantly more abundant and the proportions of genes responsible for transcription factors and phosphotransferase system were higher in ileal mucous than those in fecal samples. Brushing during colonoscopic procedure instead of using feces samples might be useful to analyze mucosa-associated microbiota.

[Duodenal obstruction after transarterial embolization for rupture of a pancreaticoduodenal artery aneurysm due to segmental arterial mediolysis:a case report].

A man in his 60s visited a local clinic because of repeated bouts of intermittent epigastric and back pain since July 2017. He was referred to our department because of suspected acute abdomen. Contrast-enhanced computed tomography revealed an aneurysm in the anterior inferior pancreaticoduodenal artery, and a retroperitoneal hematoma was observed. Although no extravascular leakage of contrast medium was observed, rupture of the aneurysm was suspected based on his vital signs, which indicated a state of shock. Emergency arteriography and coil embolization were performed. After coil embolization, the hematoma started to decrease, and no recurrent bleeding was observed. However, on hospitalization day 10, mucosal edema of the descending limb of the duodenum, thought to be an ischemic change, was observed along with gastrointestinal obstruction. A stomach tube was placed, and the patient was treated with central venous hyperalimentation for approximately 3 weeks. Because the gastrointestinal contrast radiography performed on hospitalization day 30 indicated improvement in the obstruction, liquid diet was started. Subsequently, the patient's gastrointestinal obstruction gradually improved. He was discharged on hospitalization day 47. The cause of the aneurysm in the anterior inferior pancreaticoduodenal artery was segmental arterial mediolysis (SAM). SAM is a degenerative arterial disease of unknown etiology that mainly develops in the bifurcations of the abdominal aorta. It requires immediate attention because the formation of aneurysms due to SAM can cause rupture and sudden intraperitoneal cavity bleeding. The prognosis for visceral artery aneurysms is poor, with a mortality rate of approximately 50% for cases involving pancreaticoduodenal artery aneurysm rupture. However, we believe that our experience is remarkable, as we saved our patient's life with conservative treatment involving coil embolization. Duodenal mucosal edema due to ischemic changes after coil embolization was observed, but this condition improved with conservative treatment.

Long-term retention of adalimumab treatment and associated prognostic factors for 1189 patients with Crohn's disease.

BACKGROUND AND AIM: There are few studies on the long-term efficacy of adalimumab treatment for patients with Crohn's disease. We have conducted a large, multicenter, retrospective cohort study to evaluate the long-term retention rate and prognostic factors associated with the discontinuation of adalimumab treatment in patients with Crohn's disease. METHODS: Data were collected from all patients with Crohn's disease who had received at least one induction dose of 160 mg of adalimumab between October 2010 and December 2013 at 41 institutions. The cumulative retention rates of adalimumab treatment following the first administration were estimated using the Kaplan-Meier method. Prognostic factors related to the cumulative retention rates were evaluated by log-rank tests and multivariate Cox regression analysis. RESULTS: A total of 1189 patients were included in the study. The 1-, 2-, 3-, and 4-year cumulative retention rates of adalimumab were 81%, 72%, 65%, and 62%, respectively. The multivariate Cox regression analysis confirmed female sex, previous infliximab use, perianal disease, concomitant treatment with prednisolone at baseline, higher C-reactive protein levels, and lower albumin levels as significant independent predictors of poor retention rate of adalimumab treatment. Significantly, more female patients than male patients discontinued adalimumab because of adverse events, especially skin reactions, infections, and arthralgia. CONCLUSIONS: Our data demonstrated a good retention rate of adalimumab in patients with Crohn's disease over a 4-year period. Female sex, perianal disease, concomitant treatment with prednisolone at baseline, previous infliximab use, higher C-reactive protein levels, and lower albumin levels were associated with poor retention of adalimumab treatment.

Hypergastrinemia in Long-Term Use of Proton Pump Inhibitors.

BACKGROUND/AIM: The use of proton pump inhibitors (PPIs) is known to lead to hypergastrinemia; however, the data in patients with atrophic gastritis is still lacking. The aim of this study was to investigate the effects of long-term PPIs use on the gastrin levels in patients with atrophic gastritis and to determine factors affecting hypergastrinemia in long-term users of PPIs. METHODS: Serum Helicobacter pylori IgG, gastrin and pepsinogen levels were measured. Atrophic gastritis was assessed by upper gastrointestinal endoscopies based on the Kimura-Takemoto classification and pepsinogen levels. CYP2C19 polymorphisms were assessed using DNA extracted from peripheral blood. RESULTS: A total number of 382 patients (275 men and 107 women) were enrolled. Median serum gastrin levels were higher in PPI users than in non- users (234 vs. 113 pg/mL, p < 0.001) and in women than in men (252 vs. 155 pg/mL, p = 0.006). Gastrin levels were significantly associated with corpus atrophy only in the subgroup of non-users of PPIs. Multivariate analysis revealed that hypergastrinemia (over 150 pg/mL) was significantly associated with PPI use (OR 5.30; 95% CI 3.32-8.47), women (OR 2.22; 95% CI 1.33-3.72) and corpus atrophy (OR 1.82; 95% CI 1.14-2.90). CONCLUSION: PPI use, women and corpus atrophy were risk factors for hypergastrinemia. Gender, but not corpus atrophy, affected the gastrin levels in long-term users of PPIs.

The TPH1 rs211105 gene polymorphism affects abdominal symptoms and quality of life of diarrhea-predominant irritable bowel syndrome.

The gastrointestinal symptoms of irritable bowel syndrome are strongly related to impaired quality of life (QOL), especially in diarrhea-predominant. The gene polymorphisms associated with serotonin, or 5-hydroxytryptamine, alter gastrointestinal symptoms and mental status. We aimed to evaluate the effects of gene polymorphisms on gastrointestinal symptoms, psychological conditions, and QOL, and compare these between patients with diarrhea-predominant irritable bowel syndrome (n = 62) and healthy controls (n = 64). The gene polymorphisms of 5-HTTLPR, 5-HTTVNTR, TPH1 rs453773, and TPH1 rs211105 were evaluated. Gastrointestinal symptoms, depressive state, and QOL were assessed using the Gastrointestinal Symptom Rating Scale, Self-rating Depression Scale, and Short-Form-36. Gene polymorphisms did not significantly differ in frequency between the two groups. The scores for diarrhea, abdominal pain, and indigestion significantly correlated with the physical component summary score. Only the group of patients with diarrhea-predominant irritable bowel syndrome showed a significant correlation between the TPH1 rs211105 T/T genotype and lower scores for role physical and mental health, and higher scores for indigestion and diarrhea. 5-HTTLPR l/s was associated with lower score of role emotional in the diarrhea-predominant irritable bowel syndrome and higher scores in the controls. The gene polymorphisms of 5-hydroxytryptamine signaling effected gastrointestinal symptoms and QOL, especially of the patients with diarrhea-predominant irritable bowel syndrome.

Differences in the clinical course of 516 Japanese patients with upper gastrointestinal bleeding between weekday and weekend admissions.

BACKGROUND AND AIMS: Patients suspected of having upper gastrointestinal bleeding (UGIB) admitted during the weekend tend to have a poor outcome in western countries. However, no Japanese studies have been reported on this matter. We aimed to evaluate differences in the clinical course of patients with UGIB between weekday and weekend admissions in Japan. METHODS: Medical records of patients who had undergone emergency endoscopy for UGIB were retrospectively reviewed. The severity of UGIB was evaluated using the Glasgow-Blatchford (GB) and AIMS65 score. Patients in whom UGIB was stopped and showed improved iron deficiency anemia after admission were considered as having a good clinical course. RESULTS: We reviewed 516 consecutive patients and divided them into two groups: Group A (daytime admission on a weekday: 234 patients) and Group B (nighttime or weekend admission: 282 patients). There was no significant difference in GB and AIM65 scores between the Groups. The proportions of patients with good clinical course were not significantly different between groups (A, 67.5% and B, 67.0%; p = .90). However, patients in Group B underwent hemostatic treatments more frequently compared with those in Group A (58.5% vs 47.4%, p = .012). Multivariate analysis showed that taking acid suppressants, no need for blood transfusions, use of hemostatic treatments, and GB score <12 were associated with a good clinical course. CONCLUSIONS: There were no significant differences in the clinical outcomes of patients with UGIB admitted during daytime on weekdays and those admitted at nighttime or weekends partly owing to the sufficient performance of endoscopic hemostatic treatments.

Early Intervention with Infliximab Prevents Reoperation in Crohn's Disease: A Single-Center Retrospective Analysis.

BACKGROUND/AIMS: We aimed to evaluate the prognostic factors that can aid in the prevention of first and second surgeries in patients with Crohn's disease (CD). METHODS: The clinical records of 115 patients with CD whose disease onset was between January 1987 and July 2012 were retrospectively investigated. The cumulative rate of bowel resection for CD-related intestinal manifestations following onset until the first surgery and the cumulative rate of reoperation following the first to second surgeries were estimated using the Kaplan-Meier method, and the relationship to each factor was statistically analyzed using the log-rank test. The background factors that influenced the cumulative rate of the first surgery and reoperation were evaluated using univariate and multivariate analyses. RESULTS: The cumulative bowel resection rate was significantly higher in patients with ileocolitis-type CD (p = 0.0018) and in those with CD with smoking habits (p = 0.0315). And the cumulative reoperation rate was significantly higher in patients with ileocolitis-type CD (p = 0.0161) and those without early intervention with infliximab (p = 0.0161). CONCLUSIONS: Ileocolitis-type CD and smoking habit might be initiating factors for bowel resection due to CD-related intestinal manifestations. Early intervention with infliximab likely prevents reoperation for CD recurrence.

Helicobacter pylori Eradication with Proton Pump Inhibitors or Potassium-Competitive Acid Blockers: The Effect of Clarithromycin Resistance.

BACKGROUND: Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) recently approved for Helicobacter pylori eradication therapy in Japan. AIMS: To compare PPI- and P-CAP-containing triple therapy and vonoprazan-based triple therapy. METHODS: Two hundred ninety-five initial subjects received a PPI-containing triple therapy; the next 125 subjects received vonoprazan-containing triple therapy. Two sequential groups received 7-day eradication regimens consisting of amoxicillin 750 mg, clarithromycin 200 mg both twice a day with standard dose PPI or vonoprazan (20 mg) each twice daily. H. pylori eradication was confirmed by a 13C-UBT. Clarithromycin susceptibility was evaluated by 23S rRNA PCR. RESULTS: Population cure rates with clarithromycin susceptible strains were 89.6 versus 100 % for PPI and vonoprazan therapies, respectively. Cure rates with resistant strains were 40.2 % with PPI therapy versus 76.1 % with vonoprazan triple therapy. There was no difference in side effects. CONCLUSIONS: Although 7-day P-CAB triple therapy was superior to 7-day PPI triple therapy, neither was highly effective, or can be recommended, in the presence of clarithromycin-resistant infections.

A case of Takayasu's arteritis detected in a patient with Crohn's disease following infliximab treatment.

A 19-year-old male with diarrhea, abdominal pain, fever, and elevated C-reactive protein (CRP) levels was admitted to our hospital. Endoscopic examination and small intestinal contrast radiography revealed multiple longitudinal ulcers in the large intestine and ileum. A specimen biopsied from one of these ulcers revealed non-caseating epithelioid cell granuloma. He also had a draining anal fistula. Plain chest computed tomography (CT) and abdominal contrast-enhanced CT did not reveal any vascular abnormality. A diagnosis of Crohn's disease was made, and infliximab was administered. Following infliximab administration, the diarrhea and abdominal pain disappeared, longitudinal ulcers in the large intestine healed (as evidenced by endoscopic examination), and his anal lesion improved. However, fever and elevated CRP levels persisted. With the concomitant use of prednisolone, the fever and elevation of CRP levels eventually improved, and the patient was discharged. Both, however, recurred as the patient was weaned off prednisolone treatment; consequently, he was re-hospitalized. Contrast-enhanced CT upon re-admission revealed stenoses of the right renal artery, left common carotid artery, and left subclavian artery. In addition to Crohn's disease, the patient was diagnosed with co-existing Takayasu's arteritis.

MeSH ORA framework: R/Bioconductor packages to support MeSH over-representation analysis.

BACKGROUND: In genome-wide studies, over-representation analysis (ORA) against a set of genes is an essential step for biological interpretation. Many gene annotation resources and software platforms for ORA have been proposed. Recently, Medical Subject Headings (MeSH) terms, which are annotations of PubMed documents, have been used for ORA. MeSH enables the extraction of broader meaning from the gene lists and is expected to become an exhaustive annotation resource for ORA. However, the existing MeSH ORA software platforms are still not sufficient for several reasons. RESULTS: In this work, we developed an original MeSH ORA framework composed of six types of R packages, including MeSH.db, MeSH.AOR.db, MeSH.PCR.db, the org.MeSH.XXX.db-type packages, MeSHDbi, and meshr. CONCLUSIONS: Using our framework, users can easily conduct MeSH ORA. By utilizing the enriched MeSH terms, related PubMed documents can be retrieved and saved on local machines within this framework.

PosMed: Ranking genes and bioresources based on Semantic Web Association Study.

Positional MEDLINE (PosMed; http://biolod.org/PosMed) is a powerful Semantic Web Association Study engine that ranks biomedical resources such as genes, metabolites, diseases and drugs, based on the statistical significance of associations between user-specified phenotypic keywords and resources connected directly or inferentially through a Semantic Web of biological databases such as MEDLINE, OMIM, pathways, co-expressions, molecular interactions and ontology terms. Since 2005, PosMed has long been used for in silico positional cloning studies to infer candidate disease-responsible genes existing within chromosomal intervals. PosMed is redesigned as a workbench to discover possible functional interpretations for numerous genetic variants found from exome sequencing of human disease samples. We also show that the association search engine enhances the value of mouse bioresources because most knockout mouse resources have no phenotypic annotation, but can be associated inferentially to phenotypes via genes and biomedical documents. For this purpose, we established text-mining rules to the biomedical documents by careful human curation work, and created a huge amount of correct linking between genes and documents. PosMed associates any phenotypic keyword to mouse resources with 20 public databases and four original data sets as of May 2013.

Safety of gastrointestinal endoscopic biopsy in patients taking antithrombotics.

BACKGROUND AND AIM: Current Japanese gastrointestinal (GI) endoscopic guidelines permit endoscopic biopsy without cessation of antiplatelet agents and warfarin in patients with a therapeutic range of prothrombin time-international normalized ratio (PT-INR) levels, although the evidence levels are low. We evaluated the safety of endoscopic biopsy in patients currently taking antithrombotics. METHODS: Consecutive patients receiving antithrombotics who underwent GI endoscopy from August 2012 to August 2013 were enrolled. Adverse events and endoscopic hemostasis after biopsy were evaluated. PT-INR level was measured in patients taking warfarin the day before endoscopy. RESULTS: Among 7939 patients undergoing endoscopy, 1034 patients (13.0%, 706 men and 328 women, average age 72.8 years) were receiving antithrombotics. Antithrombotics included aspirin (44.8%), warfarin (34.7%), thienopyridine (16.1%), cilostazol (10.3%), dabigatran (4.8%) etc. PT-INR levels in patients taking warfarin were >3.0 in 13 patients (4.3%), between 2.5 and 3.0 in 18 patients (6.0%), <2.5 in 269 patients (89.7%). Two hundred and six patients received endoscopic biopsy while taking aspirin (51.2%), warfarin (22.8%), and thienopyridine (13.6%). Endoscopic hemostasis was required in three patients after endoscopic biopsy (spraying thrombin in two patients, spraying thrombin and clipping in one patient). There were no major complications. The incidence of endoscopic hemostasis after biopsy in patients without antithrombotic cessation was not significantly different than in the controls not taking antithrombotics (1.5% vs 0.98%, P = 0.51). CONCLUSION: Endoscopic biopsy did not increase the bleeding risk despite not stopping antithrombotics prior to biopsy even among patients taking warfarin whose PT-INR was within the therapeutic range.

Effectiveness of a Lifestyle Improvement Support App in Combination with a Wearable Device in Japanese People with Type 2 Diabetes Mellitus: STEP-DM Study.

INTRODUCTION: Although the use of application (app)s and wearable devices supporting diabetes treatment has spread rapidly in recent years, evidence of their impact, especially in combination of them, is limited. TOMOCO™ is a lifestyle improvement support app that features interactive virtual conversations according to the programmed algorithm guiding users toward their goals of lifestyle improvement. We hypothesized that TOMOCO™ in combination with Fitbit, which accurately tracks users' activity level, would encourage people with type 2 diabetes mellitus (T2DM) to change their lifestyles and improve their glycated hemoglobin (HbA1c) levels without changes in conventional therapy. Thus, we performed the present study to explore the effectiveness of this combination in Japanese participants with T2DM who had not achieved their glycemic targets. METHODS: In this single-arm exploratory study, participants with T2DM used the TOMOCO™ and Fitbit in addition to the conventional diet/exercise therapy and anti-diabetic drug for 12 weeks. They were provided with feedback/advice by health care providers based on the TOMOCO™ and Fitbit records. The primary endpoint was the change in HbA1c from baseline to the end of the observation period. Data were expressed as mean ± standard deviation. RESULTS: Fifty-nine (96.7%) of the 61 participants (male, 42 [71.2%]; age, 60.1 ± 8.7 years; HbA1c level, 7.48 ± 0.37% at screening) completed the study. At the end of the observation period, the HbA1c was significantly reduced (- 0.41 ± 0.41%, p < 0.001). This trend was consistent across the preselected patient characteristics, including sex, age, and body mass index. However, it was more pronounced in the participants with earlier stages of behavioral changes defined by the transtheoretical model at baseline. CONCLUSIONS: The unique features of TOMOCO™ in combination with Fitbit, together with conventional therapy, may promote a healthy lifestyle and thus contribute to improving HbA1c in people with T2DM. CLINICAL TRIAL REGISTRATION: jRCT1070220007.

Different Food Preferences in Patients with Gastrointestinal Disorders.

Objective Gastrointestinal (GI) disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and inflammatory bowel disease (IBD) can exhibit overlapping GI symptoms, including abdominal pain and alterations in bowel habits. The symptoms of GI disorders are commonly considered to be triggered and exacerbated by fatty food intake. Therefore, this study aimed to compare the food preferences of patients with GI disorders. Methods Forty food images (including fatty and light foods) and 20 animal images were selected to evaluate food preferences. The preference score was assessed using a visual analog scale ranging from 1 to 100. GI symptoms were evaluated using the GI Symptom Rating Scale (GSRS), and correlations between the GSRS and preference scores were investigated. Results Overall, 22 healthy controls and 23, 29, 27, and 20 patients with FD, IBS, GERD, and IBD, respectively, were enrolled. The preference score for all foods in patients with FD was significantly lower than that in healthy controls and those with IBS, GERD, and IBD (52.9 vs. 66.5 vs. 68.5 vs. 69.1 vs. 70.7, p<0.01). The score of fatty foods was lower in patients with FD than in healthy controls and those with IBS, GERD, and IBD (43.8 vs. 72.3 vs. 77.5 vs. 77.4 vs. 80.7, p<0.01), whereas that of light foods and animal images was not different among the groups. No significant correlation was found between the preference score and symptom severity. Conclusions Patients with FD had a negative preference for foods, particularly fatty foods, independent of the severity of GI symptoms.

Practical synthesis of peptide C-terminal aldehyde on a solid support.

We have investigated practical synthetic routes for the preparation of peptide aldehyde on a solid support. Peptide aldehyde was synthesized via efficient transformation of acetal/thioacetal structures.

Semantic-JSON: a lightweight web service interface for Semantic Web contents integrating multiple life science databases.

Global cloud frameworks for bioinformatics research databases become huge and heterogeneous; solutions face various diametric challenges comprising cross-integration, retrieval, security and openness. To address this, as of March 2011 organizations including RIKEN published 192 mammalian, plant and protein life sciences databases having 8.2 million data records, integrated as Linked Open or Private Data (LOD/LPD) using SciNetS.org, the Scientists' Networking System. The huge quantity of linked data this database integration framework covers is based on the Semantic Web, where researchers collaborate by managing metadata across public and private databases in a secured data space. This outstripped the data query capacity of existing interface tools like SPARQL. Actual research also requires specialized tools for data analysis using raw original data. To solve these challenges, in December 2009 we developed the lightweight Semantic-JSON interface to access each fragment of linked and raw life sciences data securely under the control of programming languages popularly used by bioinformaticians such as Perl and Ruby. Researchers successfully used the interface across 28 million semantic relationships for biological applications including genome design, sequence processing, inference over phenotype databases, full-text search indexing and human-readable contents like ontology and LOD tree viewers. Semantic-JSON services of SciNetS.org are provided at http://semanticjson.org.

The RIKEN integrated database of mammals.

The RIKEN integrated database of mammals (http://scinets.org/db/mammal) is the official undertaking to integrate its mammalian databases produced from multiple large-scale programs that have been promoted by the institute. The database integrates not only RIKEN's original databases, such as FANTOM, the ENU mutagenesis program, the RIKEN Cerebellar Development Transcriptome Database and the Bioresource Database, but also imported data from public databases, such as Ensembl, MGI and biomedical ontologies. Our integrated database has been implemented on the infrastructure of publication medium for databases, termed SciNetS/SciNeS, or the Scientists' Networking System, where the data and metadata are structured as a semantic web and are downloadable in various standardized formats. The top-level ontology-based implementation of mammal-related data directly integrates the representative knowledge and individual data records in existing databases to ensure advanced cross-database searches and reduced unevenness of the data management operations. Through the development of this database, we propose a novel methodology for the development of standardized comprehensive management of heterogeneous data sets in multiple databases to improve the sustainability, accessibility, utility and publicity of the data of biomedical information.