Publications by authors named "Shujiro Okuda"

111 Publications

Empagliflozin maintains capillarization and improves cardiac function in a murine model of left ventricular pressure overload.

Sci Rep 2021 Sep 15;11(1):18384. Epub 2021 Sep 15.

Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Patients with type 2 diabetes treated with Sodium glucose transporter 2 (SGLT2) inhibitors show reduced mortality and hospitalization for heart failure (HF). SGLT2 inhibitors are considered to activate multiple cardioprotective pathways; however, underlying mechanisms are not fully described. This study aimed to elucidate the underlying mechanisms of the beneficial effects of SGLT2 inhibitors on the failing heart. We generated a left ventricular (LV) pressure overload model in C57BL/6NCrSlc mice by transverse aortic constriction (TAC) and examined the effects of empagliflozin (EMPA) in this model. We conducted metabolome and transcriptome analyses and histological and physiological examinations. EMPA administration ameliorated pressure overload-induced systolic dysfunction. Metabolomic studies showed that EMPA increased citrulline levels in cardiac tissue and reduced levels of arginine, indicating enhanced metabolism from arginine to citrulline and nitric oxide (NO). Transcriptome suggested possible involvement of the insulin/AKT pathway that could activate NO production through phosphorylation of endothelial NO synthase (eNOS). Histological examination of the mice showed capillary rarefaction and endothelial apoptosis after TAC, both of which were significantly improved by EMPA treatment. This improvement was associated with enhanced expression phospho-eNOS and NO production in cardiac endothelial cells. NOS inhibition attenuated these cardioprotective effects of EMPA. The in vitro studies showed that catecholamine-induced endothelial apoptosis was inhibited by NO, arginine, or AKT activator. EMPA activates the AKT/eNOS/NO pathway, which helps to suppress endothelial apoptosis, maintain capillarization and improve systolic dysfunction during LV pressure overload.
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http://dx.doi.org/10.1038/s41598-021-97787-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443662PMC
September 2021

Proposing a molecular classification associated with hypercoagulation in ovarian clear cell carcinoma.

Gynecol Oncol 2021 Aug 24. Epub 2021 Aug 24.

Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Background: Although ovarian clear cell carcinoma (CCC) is associated with high incidence of thromboembolism, the clinicopathological and biological significance of hypercoagulable status in CCC remains unclear.

Materials And Methods: We retrospectively analyzed pretreatment D-dimer levels, thromboembolic status, and clinical outcome of 125 CCCs in the discovery set and 143 CCCs in two other independent validation sets. Next, we performed RNA sequencing of 93 CCCs and compared coagulation-related gene profiles with 2492 pan-cancer data. We investigated differences in molecular characteristics of CCC subclasses based on coagulation status.

Results: In the discovery dataset, D-dimer elevation above the normal range was significantly associated with shorter progression-free and overall survival, irrespective to thromboembolic status. Multivariate analysis identified D-dimer elevation and clinical stage as an independent prognostic factors. We confirmed the prognostic significance of D-dimer elevation in the validation sets. Tissue factor and IL6, which are considered key elements of cancer-induced hypercoagulation, were highly expressed in CCC than in other cancers regardless of D-dimer level. Higher activity of various oncogenic pathways was observed in CCC with compared to without D-dimer elevation. Moreover, hierarchical cluster analysis divided 57 CCCs with D-dimer elevation into immunologically hot and cold tumor subtypes. Hot tumors were characterized by enrichment of T-cell inflamed phenotype, inflammation, the epithelial-mesenchymal transition, and high serum levels of CRP, and cold tumors by enrichment of cell cycle and MYC pathways.

Conclusions: CCC represents hypercoagulable disease and elevate D-dimer is a prognostic factor for decreased survival in CCC. D-dimer high CCC has distinct molecular characteristics into the inflammatory-driven pathway (hot tumor) and the immune-suppressive pathway (cold tumor). Treatment implication of our proposed molecular classification merits further investigation.
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http://dx.doi.org/10.1016/j.ygyno.2021.08.009DOI Listing
August 2021

Development of Novel PCR Assays for Improved Detection of Enterovirus D68.

J Clin Microbiol 2021 Aug 25:JCM0115121. Epub 2021 Aug 25.

Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Enterovirus D68 (EV-D68) causes a range of clinical manifestations, including asthma-like illness, severe respiratory disease, and acute flaccid myelitis. EV-D68 has caused worldwide outbreaks since 2014 and is now recognized as a re-emerging infection in many countries. EV-D68-specific PCR assays are widely used for the diagnosis of EV-D68 infection; however, assay sensitivity is a concern because of genetic changes in recently circulated EV-D68. To address this, we summarized EV-D68 sequences from previously reported world outbreaks from 2014 through 2020 on GenBank, and found several mutations at the primer and probe binding sites of the existing EV-D68-specific PCR assays. Subsequently, we designed two novel assays corresponding to the recently reported EV-D68 sequences: an EV-D68-specific real-time and semi-nested PCR. In an analysis of 22 EV-D68-confirmed cases during a recent EV-D68 outbreak in Japan, the new real-time PCR had higher sensitivity than the existing assay (100% vs. 45%, < 0.01) and a lower median Ct value (27.8 vs. 32.8, = 0.005). Sensitivity was higher for the new non-nested PCR (91%) than for the existing semi-nested PCR assay (50%, < 0.01). The specificity of the new real-time PCR was 100% using samples from non-EV-D68-infected cases (n = 135). In conclusion, our novel assays had higher sensitivity than the existing assay and might lead to more accurate diagnosis of recently circulating EV-D68. To prepare for future EV-D68 outbreaks, EV-D68-specific assays must be continuously monitored and updated.
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http://dx.doi.org/10.1128/JCM.01151-21DOI Listing
August 2021

Profiling of host genetic alterations and intra-tumor microbiomes in colorectal cancer.

Comput Struct Biotechnol J 2021 4;19:3330-3338. Epub 2021 Jun 4.

Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan.

Some bacteria are symbiotic in tumor tissues, and metabolites of several bacterial species have been found to cause DNA damage. However, to date, the association between bacteria and host genetic alterations in colorectal cancer (CRC) has not been fully investigated. We evaluated the association between the intra-tumor microbiome and host genetic alterations in 29 Japanese CRC patients. The tumor and non-tumor tissues were extracted from the patients, and 16S rRNA genes were sequenced for each sample. We identified enriched bacteria in tumor and non-tumor tissues. Some bacteria, such as , which is already known to be enriched in CRC, were found to be enriched in tumor tissues. Interestingly, , which is also known to be enriched in CRC, was enriched in non-tumor tissues. Furthermore, it was shown that certain bacteria that often coexist within tumor tissue were enriched in the presence of a mutated gene or signal pathway with mutated genes in the host cells. was associated with many mutated genes, as well as cell cycle-related pathways including mutated genes. In addition, the patients with a high abundance of were suggested to be associated with mutational signature 3 indicating failure of double-strand DNA break repairs. These results suggest that CRC development may be partly caused by DNA damage caused by substances released by bacterial infection. Taken together, the identification of distinct gut microbiome patterns and their host specific genetic alterations might facilitate targeted interventions, such as modulation of the microbiome in addition to anticancer agents or immunotherapy.
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http://dx.doi.org/10.1016/j.csbj.2021.05.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202188PMC
June 2021

Obesity-Related Gut Microbiota Aggravates Alveolar Bone Destruction in Experimental Periodontitis through Elevation of Uric Acid.

mBio 2021 06 1;12(3):e0077121. Epub 2021 Jun 1.

Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.

Obesity is a risk factor for periodontal disease (PD). Initiation and progression of PD are modulated by complex interactions between oral dysbiosis and host responses. Although obesity is associated with increased susceptibility to bacterial infection, the detailed mechanisms that connect obesity and susceptibility to PD remain elusive. Using fecal microbiota transplantation and a ligature-induced PD model, we demonstrated that gut dysbiosis-associated metabolites from high-fat diet (HFD)-fed mice worsen alveolar bone destruction. Fecal metabolomics revealed elevated purine degradation pathway activity in HFD-fed mice, and recipient mice had elevated levels of serum uric acid upon PD induction. Furthermore, PD induction caused more severe bone destruction in hyperuricemic than normouricemic mice, and the worsened bone destruction was completely abrogated by allopurinol, a xanthine oxidase inhibitor. Thus, obesity increases the risk of PD by increasing production of uric acid mediated by gut dysbiosis. Obesity is an epidemic health issue with a rapid increase worldwide. It increases the risk of various diseases, including periodontal disease, an oral chronic infectious disease. Although obesity increases susceptibility to bacterial infection, the precise biological mechanisms that link obesity and susceptibility to periodontal disease remain elusive. Using fecal microbial transplantation, experimental periodontitis, and metabolomics, our study demonstrates uric acid as a causative substance for greater aggravation of alveolar bone destruction in obesity-related periodontal disease. Gut microbiota from obese mice upregulated the purine degradation pathway, and the resulting elevation of serum uric acid promoted alveolar bone destruction. The effect of uric acid was confirmed by administration of allopurinol, an inhibitor of xanthine oxidase. Overall, our study provides new insights into the pathogenic mechanisms of obesity-associated periodontal disease and the development of new therapeutic options for the disease.
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http://dx.doi.org/10.1128/mBio.00771-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262938PMC
June 2021

Extracellular DNA of slow growers of mycobacteria and its contribution to biofilm formation and drug tolerance.

Sci Rep 2021 May 26;11(1):10953. Epub 2021 May 26.

Department of Bacteriology, Niigata University School of Medicine, 1-757, Asahimachi-Dori, Chuo-ku, Niigata, Niigata, 951-9510, Japan.

DNA is basically an intracellular molecule that stores genetic information and carries instructions for growth and reproduction in all cellular organisms. However, in some bacteria, DNA has additional roles outside the cells as extracellular DNA (eDNA), which is an essential component of biofilm formation and hence antibiotic tolerance. Mycobacteria include life-threating human pathogens, most of which are slow growers. However, little is known about the nature of pathogenic mycobacteria's eDNA. Here we found that eDNA is present in slow-growing mycobacterial pathogens, such as Mycobacterium tuberculosis, M. intracellulare, and M. avium at exponential growth phase. In contrast, eDNA is little in all tested rapid-growing mycobacteria. The physiological impact of disrupted eDNA on slow-growing mycobacteria include reduced pellicle formation, floating biofilm, and enhanced susceptibility to isoniazid and amikacin. Isolation and sequencing of eDNA revealed that it is identical to the genomic DNA in M. tuberculosis and M. intracellulare. In contrast, accumulation of phage DNA in eDNA of M. avium, suggests that the DNA released differs among mycobacterial species. Our data show important functions of eDNA necessary for biofilm formation and drug tolerance in slow-growing mycobacteria.
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http://dx.doi.org/10.1038/s41598-021-90156-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155028PMC
May 2021

Histopathological characteristics and artificial intelligence for predicting tumor mutational burden-high colorectal cancer.

J Gastroenterol 2021 Jun 28;56(6):547-559. Epub 2021 Apr 28.

Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.

Background: Tumor mutational burden-high (TMB-H), which is detected with gene panel testing, is a promising biomarker for immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC). However, in clinical practice, not every patient is tested for TMB-H using gene panel testing. We aimed to identify the histopathological characteristics of TMB-H CRC for efficient selection of patients who should undergo gene panel testing. Moreover, we attempted to develop a convolutional neural network (CNN)-based algorithm to predict TMB-H CRC directly from hematoxylin and eosin (H&E) slides.

Methods: We used two CRC cohorts tested for TMB-H, and whole-slide H&E digital images were obtained from the cohorts. The Japanese CRC (JP-CRC) cohort (N = 201) was evaluated to detect the histopathological characteristics of TMB-H using H&E slides. The JP-CRC cohort and The Cancer Genome Atlas (TCGA) CRC cohort (N = 77) were used to develop a CNN-based TMB-H prediction model from the H&E digital images.

Results: Tumor-infiltrating lymphocytes (TILs) were significantly associated with TMB-H CRC (P < 0.001). The area under the curve (AUC) for predicting TMB-H CRC was 0.910. We developed a CNN-based TMB-H prediction model. Validation tests were conducted 10 times using randomly selected slides, and the average AUC for predicting TMB-H slides was 0.934.

Conclusions: TILs, a histopathological characteristic detected with H&E slides, are associated with TMB-H CRC. Our CNN-based model has the potential to predict TMB-H CRC directly from H&E slides, thereby reducing the burden on pathologists. These approaches will provide clinicians with important information about the applications of ICIs at low cost.
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http://dx.doi.org/10.1007/s00535-021-01789-wDOI Listing
June 2021

Three-dimensional understanding of the morphological complexity of the human uterine endometrium.

iScience 2021 Apr 2;24(4):102258. Epub 2021 Mar 2.

Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.

The fundamental morphology of the endometrial glands is not sufficiently understood by 2D observation because these glands have complicated winding and branching patterns. To construct a large picture of the endometrial gland structure, we performed tissue-clearing-based 3D imaging of human uterine endometrial tissue. Our 3D immunohistochemistry and layer analyses revealed that the endometrial glands form a plexus network in the stratum basalis and expand horizontally along the muscular layer, similar to the rhizome of grass. We then extended our method to assess the 3D morphology of tissue affected by adenomyosis, a representative "endometrium-related disease," and observed its 3D morphological features, including the direct invasion of endometrial glands into the myometrium and an ant colony-like network of ectopic endometrial glands within the myometrium. Thus, further understanding of the morphology of the human endometrium based on 3D analysis will lead to the identification of the pathogenesis of endometrium-related diseases.
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http://dx.doi.org/10.1016/j.isci.2021.102258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995615PMC
April 2021

Adipose most abundant 2 protein is a predictive marker for cisplatin sensitivity in cancers.

Sci Rep 2021 03 18;11(1):6255. Epub 2021 Mar 18.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.

Cisplatin (CDDP) is one of the chemotherapeutic drugs being used to treat various cancers. Although effective in many cases, as high doses of CDDP cause cytotoxic effects that may worsen patients' condition, therefore, a marker of sensitivity to CDDP is necessary to enhance the safety and efficiency of CDDP administration. This study focused on adipose most abundant 2 (APM2) to examine its potential as a marker of CDDP sensitivity. The relationship of APM2 expression with the mechanisms of CDDP resistance was examined in vitro and in vivo using hepatocellular carcinoma (HCC) cells, tissues and serum of HCC patients (n = 71) treated initially with intrahepatic arterial infusion of CDDP followed by surgical resection. The predictability of serum APM2 for CDDP sensitivity was assessed in additional 54 HCC patients and 14 gastric cancer (GC) patients. APM2 expression in CDDP-resistant HCC was significantly higher both in serum and the tissue. Bioinformatic analyses and histological analyses demonstrated upregulation of ERCC6L (DNA excision repair protein ERCC6-like) by APM2, which accounts for the degree of APM2 expression. The serum APM2 level and chemosensitivity for CDDP were assessed and cut-off value of serum APM2 for predicting the sensitivity to CDDP was determined to be 18.7 µg/mL. The value was assessed in HCC (n = 54) and GC (n = 14) patients for its predictability of CDDP sensitivity, resulted in predictive value of 77.3% and 100%, respectively. Our study demonstrated that APM2 expression is related to CDDP sensitivity and serum APM2 can be an effective biomarker of HCC and GC for determining the sensitivity to CDDP.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028487).
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http://dx.doi.org/10.1038/s41598-021-85498-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973578PMC
March 2021

Mutational signatures in squamous cell carcinoma of the lung.

J Thorac Dis 2021 Feb;13(2):1075-1082

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Tumor mutational burden (TMB) has been identified as one of the predictors for the response to anti-programmed cell death-1 (anti-PD-1) antibody therapy and reported to correlate with smoking history in lung adenocarcinoma. However, in squamous cell carcinoma of the lung, the association between TMB and clinicopathological background factors, such as smoking history, has not been reported, including in our previous study. The mutational signature is a tool to identify the mutagens that are contributing to the mutational spectrum of a tumor by investigating the pattern of DNA changes. Here, we analyzed the mutational signature in lung squamous cell carcinoma to identify mutagens affecting the TMB.

Methods: Seven representative mutational signatures including signature 7 (SI7) [ultraviolet (UV)-related], SI4 (smoking), SI6/15 [mismatch repair (MMR)], SI2/13 [apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)], and SI5 (clock-like) were analyzed in Japanese patients with lung squamous cell carcinoma (n=67) using data generated by next-generation sequencing consisting of a 415-gene panel. The relationships between signatures and clinico-pathological data including TMB and programmed death-ligand 1 (PD-L1) expression were analyzed.

Results: Although the reconstructed mutational counts were small with targeted sequencing (median: 30.1, range: 13.3-98.7), the distributions of signatures were comparable among samples, with 56 cases containing more than four signatures. The smoking-related SI4 was found in 45 cases and was significantly related with pack-year index (PYI) (P=0.026). The reconstructed mutation counts were highly correlated with SI4 (r=0.51, P<0.0001), whereas the correlation was weak with SI6/15 (MMR-related) and SI2/13 (APOBEC-related). There was no mutational signature related with PD-L1 expression. Some patients exhibited unique signatures; the patient with the highest mutational counts had a MMR signature, and another patient with a prominent UV signature had occupational exposure to UV, as he was employed as a neon sign engineer.

Conclusions: Mutational signatures can predict the cause of lung squamous cell carcinoma. Tobacco smoking is the mutagen most related with TMB.
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http://dx.doi.org/10.21037/jtd-20-2602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947495PMC
February 2021

The jPOST Repository as a Public Data Repository for Shotgun Proteomics.

Methods Mol Biol 2021 ;2259:309-322

Division of bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

In recent years, mass spectrometry-based proteomics approach has made significant progress and the number of datasets related to various proteomics projects has increased worldwide. To promote the sharing and reuse of promising datasets, it is important to build an appropriate, high-quality public data repository. For this purpose, several repositories have already been created. The jPOST repository that we developed in 2016 has successfully implemented several unique features, such as fast file upload, flexible file management, and an easy-to-use interface. In addition, this repository is an official member of the ProteomeXchange Consortium established to facilitate standard data submission and global dissemination of mass spectrometry proteomics data. Our repository contributes to the global partnership for sharing and storing all the datasets related to various proteomics experiments.
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http://dx.doi.org/10.1007/978-1-0716-1178-4_20DOI Listing
April 2021

Activin a Receptor Type 2A Mutation Affects the Tumor Biology of Microsatellite Instability-High Gastric Cancer.

J Gastrointest Surg 2021 Jan 8. Epub 2021 Jan 8.

Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.

Background: Activin A receptor type 2A (ACVR2A) is one of the most frequently mutated genes in microsatellite instability-high (MSI-H) gastric cancer. However, the clinical relevance of the ACVR2A mutation in MSI-H gastric cancer patients remains unclear. The aims of this study were to explore the effect of ACVR2A mutation on the tumor behavior and to identify the clinicopathological characteristics of gastric cancer patients with ACVR2A mutations.

Methods: An in vitro study was performed to investigate the biological role of ACVR2A via CRISPR/Cas9-mediated ACVR2A knockout MKN74 human gastric cancer cells. One hundred twenty-four patients with gastric cancer were retrospectively analyzed, and relations between MSI status, ACVR2A mutations, and clinicopathological factors were evaluated.

Results: ACVR2A knockout cells showed less aggressive tumor biology than mock-transfected cells, displaying reduced proliferation, migration, and invasion (P < 0.05). MSI mutations were found in 10% (13/124) of gastric cancer patients, and ACVR2A mutations were found in 8.1% (10/124) of patients. All ACVR2A mutations were accompanied by MSI. The 5-year overall survival rates of ACVR2A wild-type patients and ACVR2A-mutated patients were 57% and 90%, respectively (P = 0.048). Multivariate analysis revealed that older age (P = 0.015), distant metastasis (P < 0.001), and ACVR2A wild-type status (P = 0.040) were independent prognostic factors for overall survival.

Conclusions: Our study demonstrated that gastric cancer patients with ACVR2A mutation have a significantly better prognosis than those without. Dysfunction of ACVR2A in MKN74 human gastric cancer cells caused less aggressive tumor biology, indicating the importance of ACVR2A in the progression of MSI-H tumors.
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http://dx.doi.org/10.1007/s11605-020-04889-9DOI Listing
January 2021

p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response.

Nat Commun 2021 01 4;12(1):16. Epub 2021 Jan 4.

Department of Physiology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, 113-8421, Japan.

Autophagy contributes to the selective degradation of liquid droplets, including the P-Granule, Ape1-complex and p62/SQSTM1-body, although the molecular mechanisms and physiological relevance of selective degradation remain unclear. In this report, we describe the properties of endogenous p62-bodies, the effect of autophagosome biogenesis on these bodies, and the in vivo significance of their turnover. p62-bodies are low-liquidity gels containing ubiquitin and core autophagy-related proteins. Multiple autophagosomes form on the p62-gels, and the interaction of autophagosome-localizing Atg8-proteins with p62 directs autophagosome formation toward the p62-gel. Keap1 also reversibly translocates to the p62-gels in a p62-binding dependent fashion to activate the transcription factor Nrf2. Mice deficient for Atg8-interaction-dependent selective autophagy show that impaired turnover of p62-gels leads to Nrf2 hyperactivation in vivo. These results indicate that p62-gels are not simple substrates for autophagy but serve as platforms for both autophagosome formation and anti-oxidative stress.
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http://dx.doi.org/10.1038/s41467-020-20185-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782522PMC
January 2021

Gallincin ameliorates colitis-associated inflammation and barrier function in mice based on network pharmacology prediction.

J Int Med Res 2020 Dec;48(12):300060520951023

Department of Gastroenterology, Guizhou Provincial People's Hospital, Guiyang, China.

Objective: To explore potential mechanisms and effects of gallincin on a mouse model of colitis induced by dextran sulfate sodium (DSS).

Methods: Network pharmacology analysis was used to predict the molecular mechanism of action of gallincin for treatment of colitis. Gallincin was administered orally to mice with DSS-induced colitis. Expression of tumor necrosis factor α (TNF-α), D-lactate, and interleukin-1β (IL-1β) and myeloperoxidase activity were assessed with real-time quantitative PCR and an enzyme-linked immunoassay, respectively. Expression of occludin, zonula occludens 1 (ZO-1), and phosphorylated extracellular signal-regulated protein kinase1/2 (p-ERK1/2) was analyzed with immunohistochemical staining and/or western blot assays.

Results: Using a network pharmacology approach, 12 mapping targets between gallincin and colitis were obtained, including ERK/mitogen-activated protein kinase. Further investigations in an experimental colitis mouse model showed that gallincin significantly ameliorated experimental colitis, reduced D-lactate levels, and remarkably increased occludin and ZO-1 expression, possibly in part by decreasing IL-1β, TNF-α, and p-ERK1/2 levels and inhibiting leukocyte penetration.

Conclusions: Gallincin regulated colonic barrier function and reduced colitis-associated inflammation, suggesting it is a promising drug for the treatment of ulcerative colitis.
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http://dx.doi.org/10.1177/0300060520951023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745594PMC
December 2020

Genetic profiling for diffuse type and genomically stable subtypes in gastric cancer.

Comput Struct Biotechnol J 2020 29;18:3301-3308. Epub 2020 Oct 29.

Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan.

Gastric cancer is one of the most common and clinically important diseases worldwide. The traditional Laeuren classification divides gastric cancer into two histopathological subtypes: diffuse and intestinal. Recent cancer genomics research has led to the development of a new classification based on molecular characteristics. The newly defined genomically stable (GS) subtype shares many cases with the histopathologically diffuse type. In this study, we performed genetic profiling of recurrently and significantly mutated genes in diffuse type and GS subtype tumors. We observed significantly different genetic characteristics, although the two subtypes overlapped in many cases. In addition, based on the profiles of the significantly mutated genes, we identified molecular functions and mutational signatures characteristic of each subtype. These results will advance the clinical application of the diffuse type and GS subtype gastric cancer in precision medicine for treating gastric cancer.
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http://dx.doi.org/10.1016/j.csbj.2020.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666323PMC
October 2020

GlycoPOST realizes FAIR principles for glycomics mass spectrometry data.

Nucleic Acids Res 2021 01;49(D1):D1523-D1528

Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan.

For the reproducibility and sustainability of scientific research, FAIRness (Findable, Accessible, Interoperable and Re-usable), with respect to the release of raw data obtained by researchers, is one of the most important principles underpinning the future of open science. In genomics and transcriptomics, the sharing of raw data from next-generation sequencers is made possible through public repositories. In addition, in proteomics, the deposition of raw data from mass spectrometry (MS) experiments into repositories is becoming standardized. However, a standard repository for such MS data had not yet been established in glycomics. With the increasing number of glycomics MS data, therefore, we have developed GlycoPOST (https://glycopost.glycosmos.org/), a repository for raw MS data generated from glycomics experiments. In just the first year since the release of GlycoPOST, 73 projects have already been registered by researchers around the world, and the number of registered projects is continuously growing, making a significant contribution to the future FAIRness of the glycomics field. GlycoPOST is a free resource to the community and accepts (and will continue to accept in the future) raw data regardless of vendor-specific formats.
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http://dx.doi.org/10.1093/nar/gkaa1012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778884PMC
January 2021

Frequent Germline and Somatic Single Nucleotide Variants in the Promoter Region of the Ribosomal RNA Gene in Japanese Lung Adenocarcinoma Patients.

Cells 2020 11 3;9(11). Epub 2020 Nov 3.

Histopathology Core Facility, Niigata University Faculty of Medicine, Niigata 951-8510, Japan.

Ribosomal RNA (rRNA), the most abundant non-coding RNA species, is a major component of the ribosome. Impaired ribosome biogenesis causes the dysfunction of protein synthesis and diseases called "ribosomopathies," including genetic disorders with cancer risk. However, the potential role of rRNA gene (rDNA) alterations in cancer is unknown. We investigated germline and somatic single-nucleotide variants (SNVs) in the rDNA promoter region (positions -248 to +100, relative to the transcription start site) in 82 lung adenocarcinomas (LUAC). Twenty-nine tumors (35.4%) carried germline SNVs, and eight tumors (9.8%) harbored somatic SNVs. Interestingly, the presence of germline SNVs between positions +1 and +100 ( = 12; 14.6%) was associated with significantly shorter recurrence-free survival (RFS) and overall survival (OS) by univariate analysis ( < 0.05, respectively), and was an independent prognostic factor for RFS and OS by multivariate analysis. LUAC cell line PC9, carrying rDNA promoter SNV at position +49, showed significantly higher ribosome biogenesis than H1650 cells without SNV. Upon nucleolar stress induced by actinomycin D, PC9 retained significantly higher ribosome biogenesis than H1650. These results highlight the possible functional role of SNVs at specific sites of the rDNA promoter region in ribosome biogenesis, the progression of LUAC, and their potential prognostic value.
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http://dx.doi.org/10.3390/cells9112409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692307PMC
November 2020

Higher genome mutation rates of Beijing lineage of Mycobacterium tuberculosis during human infection.

Sci Rep 2020 10 22;10(1):17997. Epub 2020 Oct 22.

Department of Bacteriology, Niigata University School of Medicine, 1-757, Asahimachi-Dori, Chuo-ku, Niigata, Niigata, 951-9510, Japan.

Mycobacterium tuberculosis (Mtb) strains of Beijing lineage have caused great concern because of their rapid emergence of drug resistance and worldwide spread. DNA mutation rates that reflect evolutional adaptation to host responses and the appearance of drug resistance have not been elucidated in human-infected Beijing strains. We tracked and obtained an original Mtb isolate of Beijing lineage from the 1999 tuberculosis outbreak in Japan, as well as five other isolates that spread in humans, and two isolates from the patient caused recurrence. Three isolates were from patients who developed TB within one year after infection (rapid-progressor, RP), and the other three isolates were from those who developed TB more than one year after infection (slow-progressor, SP). We sequenced genomes of these isolates and analyzed the propensity and rate of genomic mutations. Generation time versus mutation rate curves were significantly higher for RP. The ratio of oxidative versus non-oxidation damages induced mutations was higher in SP than RP, suggesting that persistent Mtb are exposed to oxidative stress in the latent state. Our data thus demonstrates that higher mutation rates of Mtb Beijing strains during human infection is likely to account for the higher adaptability and an emergence ratio of drug resistance.
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http://dx.doi.org/10.1038/s41598-020-75028-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582865PMC
October 2020

Sphingosine Kinase 1 is Associated With Immune Cell-Related Gene Expressions in Human Breast Cancer.

J Surg Res 2020 12 15;256:645-656. Epub 2020 Aug 15.

Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan.

Background: Although previous experiments have implicated sphingosine-1-phosphate (S1P) as a links between immune reactions and cancer progression, the exact mechanism of this interaction has not comprehensively studied in clinical human samples. This study sought to evaluate the S1P regulation by sphingosine kinase 1 (SPHK1), an S1P-producing enzyme, in the immunity/immuno-reactivity of clinical human breast cancer surgical specimens.

Methods: S1P levels were examined in tumor, peritumoral, and normal human breast samples using mass spectrometry. Genomics Data Commons data portal of The Cancer Genome Atlas cohort was used to assess the expression of S1P-related and immune-related genes.

Results: S1P levels were significantly higher in tumor samples compared to peritumoral (P < 0.05) or normal human breast samples (P < 0.001). SPHK1 gene expression was elevated in tumoral samples compared to normal breast samples (P < 0.01). Furthermore, the elevated expression of SPHK1 in breast cancer tissue was associated with an increased expression of the different kinds of immune-related genes, such as CD68, CD163, CD4, and FOXP3 (forkhead box P3), in HER2-negative breast cancer. Network analysis showed the central role of SPHK1 in the interaction of S1P signaling and expression of immune cell-related proteins.

Conclusions: We demonstrated that S1P is mainly produced by tumor tissue, rather than peritumoral tissue, in breast cancer patients. Our data revealed the involvement of S1P signaling in the regulation of immune-related genes, suggesting the links between S1P and complicated immune-cancer interactions in breast cancer patients.
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http://dx.doi.org/10.1016/j.jss.2020.06.057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882641PMC
December 2020

Verification of the Japanese staging system for rectal cancer, focusing on differences with the TNM classification.

Surg Today 2020 Nov 22;50(11):1443-1451. Epub 2020 May 22.

Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan.

Purpose: The 9th Japanese Classification of Colorectal Cancer (9th JSCCR) has two main differences from the TNM classification (8th AJCC): first, main or lateral lymph node metastasis is classified as jN3; second, tumor nodules (ND) are treated as lymph node metastasis. In this study, we verified the 9th JSCCR for rectal cancer, focusing on the differences with the 8th AJCC.

Methods: This retrospective analysis involved 212 patients with stage I-III rectal cancer. ND was evaluated using whole-mount sections. We evaluated the relapse-free survival of each staging system, and compared the prognostic significance of the different staging systems using the Akaike information criterion (AIC) and Harrell's concordance index (c-index).

Results: Main or lateral lymph node metastasis was detected in nine of 212 (4%) patients. ND was detected in 79 of 212 (37%) patients. The best risk stratification power was observed in the 9th JSCCR (AIC, 759; c-index, 0.708) compared with the 7th JSCCR (AIC, 771; c-index, 0.681), 8th JSCCR (AIC, 768; c-index, 0.696), and the 8th AJCC (AIC, 766; c-index, 0.691).

Conclusions: The 9th JSCCR, which includes the concepts of jN3 and ND, is useful for the risk stratification of rectal cancer, and the contributes to precise decision-making for follow-up management and adjuvant therapy.
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http://dx.doi.org/10.1007/s00595-020-02024-4DOI Listing
November 2020

BioHackathon 2015: Semantics of data for life sciences and reproducible research.

F1000Res 2020 24;9:136. Epub 2020 Feb 24.

St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, Australia.

We report on the activities of the 2015 edition of the BioHackathon, an annual event that brings together researchers and developers from around the world to develop tools and technologies that promote the reusability of biological data. We discuss issues surrounding the representation, publication, integration, mining and reuse of biological data and metadata across a wide range of biomedical data types of relevance for the life sciences, including chemistry, genotypes and phenotypes, orthology and phylogeny, proteomics, genomics, glycomics, and metabolomics. We describe our progress to address ongoing challenges to the reusability and reproducibility of research results, and identify outstanding issues that continue to impede the progress of bioinformatics research. We share our perspective on the state of the art, continued challenges, and goals for future research and development for the life sciences Semantic Web.
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http://dx.doi.org/10.12688/f1000research.18236.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141167PMC
February 2021

Phosphoproteomic and bioinformatic methods for analyzing signaling in vertebrate axon growth and regeneration.

J Neurosci Methods 2020 06 8;339:108723. Epub 2020 Apr 8.

Departments of Laboratory of Bioinformatics, School and Medicine and Graduate School of Medical/Dental Sciences, Japan.

Phosphorylation is the most important post-translational modification of proteins in many cells, including neurons. Phosphoproteomics is a relatively new technique for comprehensively identifying phosphorylation sites in the whole proteome of a given system. We applied this method to developmental neurobiology research to understand the signaling pathways that regulate the mammalian growth cone, which is formed at the tips of developing neurites to ensure accurate neuronal network formation. Using this powerful technique, we identified at least four phosphorylation sites tightly associated with axon growth. Because phosphoproteomic results include relatively large numbers of phosphopeptides, the data are typically analyzed using bioinformatics. We utilized three bioinformatics tools to identify the responsible protein kinases, the putative functions of the phosphorylated protein groups, and the evolutional aspects of the phosphorylated proteins. Collectively, these data indicate phosphoproteomics is a cutting-edge tool for neuroscience research.
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http://dx.doi.org/10.1016/j.jneumeth.2020.108723DOI Listing
June 2020

RNF43 mutation is associated with aggressive tumor biology along with BRAF V600E mutation in right-sided colorectal cancer.

Oncol Rep 2020 Jun 23;43(6):1853-1862. Epub 2020 Mar 23.

Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan.

Right-sided colorectal cancer (RCRC) demonstrates worse survival outcome compared with left-sided CRC (LCRC). Recently, the importance of RNF43 mutation and BRAF V600E mutation has been reported in the serrated neoplasia pathway, which is one of the precancerous lesions in RCRC. It was hypothesized that the clinical significance of RNF43 mutation differs according to primary tumor sidedness. To test this hypothesis, the clinicopathological characteristics and survival outcome of patients with RNF43 mutation in RCRC and LCRC were investigated. Stage I-IV CRC patients (n=201) were analyzed. Genetic alterations including RNF43 using a 415-gene panel were investigated. Clinicopathological characteristics between RNF43 wild-type and RNF43 mutant-type were analyzed. Moreover, RNF43 mutant-type was classified according to primary tumor sidedness, i.e., right-sided RNF43 mutant-type or left-sided RNF43 mutant-type, and the clinicopathological characteristics between the two groups were compared. RNF43 mutational prevalence, spectrum and frequency between our cohort and TCGA samples were compared. RNF43 mutation was observed in 27 out of 201 patients (13%). Multivariate analysis revealed that age (≥65), absence of venous invasion, and BRAF V600E mutation were independently associated with RNF43 mutation. Among the 27 patients with RNF43 mutation, 12 patients were right-sided RNF43 mutant-type and 15 left-sided RNF43 mutant-type. Right-sided RNF43 mutant-type was significantly associated with histopathological grade 3, presence of lymphatic invasion, APC wild, BRAF V600E mutation, microsatellite instability-high (MSI-H), and RNF43 nonsense/frameshift mutation compared with left-sided RNF43 mutant-type. Similarly, RNF43 nonsense/frameshift mutations were more frequently observed in RCRC compared with LCRC in the TCGA cohort (P=0.042). Right-sided RNF43 mutant-type exhibited significantly worse overall survival than RNF43 wild-type and left-sided RNF43 mutant-type (P=0.001 and P=0.023, respectively) in stage IV disease. RNF43 mutation may be a distinct molecular subtype which is associated with aggressive tumor biology along with BRAF V600E mutation in RCRC.
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http://dx.doi.org/10.3892/or.2020.7561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160543PMC
June 2020

Innate Immune Responses in Serum and Cerebrospinal Fluid From Neonates and Infants Infected With Parechovirus-A3 or Enteroviruses.

J Infect Dis 2020 07;222(4):681-689

Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Background: Parechovirus (PeV)-A3 and enteroviruses (EV) are the most common viruses causing sepsis and meningoencephalitis in neonates and young infants. Clinical manifestations of PeV-A3 infection are more severe than those of EV infection, and no pleocytosis with a positive polymerase chain reaction (PCR) result for PeV-A3 in cerebrospinal fluid (CSF) are characteristic findings. We hypothesized that innate immune responses to PeV-A3 and EV are distinct in serum and CSF.

Methods: We evaluated 22 cytokines/chemokines in serum and CSF from PeV-A3- or EV-infected patients younger than 4 months in Niigata, Japan, from 2015 through 2018. Infection was diagnosed with real-time PCR followed by sequencing. Febrile neonates and infants with sepsis-like syndrome who had negative bacterial culture and viral PCR for both PeV-A and EV were also included (non-PeV-A/EV patients).

Results: Among 192 febrile patients, we evaluated 16 PeV-A3-infected, 15 EV-infected, and 8 non-PeV-A/EV patients. Serum pro-/anti-inflammatory cytokine/chemokine levels were higher in PeV-A3-infected patients than in EV-infected patients (P < .02). Although most cytokine/chemokine were elevated in CSF from EV-infected patients, levels were low or undetectable in PeV-A3-infected and non-PeV-A/EV patients (P < .001).

Conclusions: Distinct cytokine/chemokine patterns in serum and CSF may explain the different clinical manifestations of PeV-A3-infected and EV-infected neonates and young infants.
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http://dx.doi.org/10.1093/infdis/jiaa131DOI Listing
July 2020

XCL1 expression correlates with CD8-positive T cells infiltration and PD-L1 expression in squamous cell carcinoma arising from mature cystic teratoma of the ovary.

Oncogene 2020 04 2;39(17):3541-3554. Epub 2020 Mar 2.

Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.

Molecular characteristics of carcinoma arising from mature cystic teratoma of the ovary (MCT) remain unclear due to its rarity. We analyzed RNA-sequencing data of 2322 pan-cancer [1378 squamous cell carcinomas (SCC), 6 adenosquamous carcinomas (ASC), and 938 adenocarcinomas (AC)] including six carcinomas arising from MCT (four SCCs, one ASC, and one AC). Hierarchical clustering and principal component analysis showed that gene expression profiles of carcinomas arising from MCT were different between each histological type and that gene expression profiles of SCCs arising MCT (MCT-SCCs) was apparently similar to those of lung SCCs. By epidermis-associated pathways activity based on gene set enrichment analysis, 1030 SCCs were divided into two groups: epidermis-signature high (head and neck, esophagus, and skin) and low (cervix, lung, and MCT). In addition to pan-SCC transcriptome analysis, cytokeratin profiling based on immunohistochemistry in the independent samples of 21 MCT-SCCs clarified that MCT-SCC dominantly expressed CK18, suggesting the origin of MCT-SCC was columnar epithelium. Subsequently, we investigated differentially expressed genes in MCT-SCCs compared with different SCCs and identified XCL1 was specifically overexpressed in MCT-SCCs. Through immunohistochemistry analysis, we identified XCL1 expression on tumor cells in 13/24 (54%) of MCT-SCCs but not in MCTs. XCL1 expression was also significantly associated with the number of tumor-infiltrating CD8-positive T cells and PD-L1 expression on tumor cells. XCL1 produced by tumor cells may induce PD1/PD-L1 interaction and dysfunction of CD8-positive T cells in tumor microenvironment. XCL1 expression may be a novel biomarker for malignant transformation of MCT into SCC and a biomarker candidate for therapeutic response to an anti-PD1/PD-L1 therapy.
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http://dx.doi.org/10.1038/s41388-020-1237-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176584PMC
April 2020

Rice Endosperm Protein Administration to Juvenile Mice Regulates Gut Microbiota and Suppresses the Development of High-Fat Diet-Induced Obesity and Related Disorders in Adulthood.

Nutrients 2019 Dec 2;11(12). Epub 2019 Dec 2.

Department of Applied Molecular Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan.

Obesity and related disorders, which are increasing in adults worldwide, are closely linked to childhood diet and are associated with chronic inflammation. Rice endosperm protein (REP) intake during adulthood has been reported to improve lipid metabolism and suppress the progression of diabetic kidney disease in animal models. However, the effects of REP intake during childhood on adulthood health are unclear. Therefore, we used a mouse model to experimentally investigate the preconditioning effects of REP intake during childhood on the development of obesity and related disorders in adulthood. Male C57BL/6J mice were pair-fed a normal-fat diet containing casein or REP during the juvenile period and then a high-fat diet (HFD) containing casein or REP during adulthood. Mice fed REP during the juvenile period showed better body weight, blood pressure, serum lipid profiles, lipopolysaccharide (LPS)-binding protein levels, and glucose tolerance in adulthood than those fed casein during the juvenile period. HFD-induced renal tubulo-glomerular alterations and hepatic microvesicular steatosis were less evident in REP-fed mice than in casein-fed ones. REP intake during the juvenile period improved HFD-induced dysbiosis (i.e., genus proliferation and reduced gut microbiota diversity), thereby suppressing endotoxin-related chronic inflammation. Indeed, REP-derived peptides showed antibacterial activity against , a major producer of LPS. In conclusion, REP supplementation during the juvenile period may regulate the gut microbiota and thus suppress the development of obesity and related disorders in adulthood in mice.
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http://dx.doi.org/10.3390/nu11122919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950226PMC
December 2019

The ProteomeXchange consortium in 2020: enabling 'big data' approaches in proteomics.

Nucleic Acids Res 2020 01;48(D1):D1145-D1152

European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.

The ProteomeXchange (PX) consortium of proteomics resources (http://www.proteomexchange.org) has standardized data submission and dissemination of mass spectrometry proteomics data worldwide since 2012. In this paper, we describe the main developments since the previous update manuscript was published in Nucleic Acids Research in 2017. Since then, in addition to the four PX existing members at the time (PRIDE, PeptideAtlas including the PASSEL resource, MassIVE and jPOST), two new resources have joined PX: iProX (China) and Panorama Public (USA). We first describe the updated submission guidelines, now expanded to include six members. Next, with current data submission statistics, we demonstrate that the proteomics field is now actively embracing public open data policies. At the end of June 2019, more than 14 100 datasets had been submitted to PX resources since 2012, and from those, more than 9 500 in just the last three years. In parallel, an unprecedented increase of data re-use activities in the field, including 'big data' approaches, is enabling novel research and new data resources. At last, we also outline some of our future plans for the coming years.
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http://dx.doi.org/10.1093/nar/gkz984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145525PMC
January 2020

The Human Gut Microbiome is Structured to Optimize Molecular Interaction Networks.

Comput Struct Biotechnol J 2019 29;17:1040-1046. Epub 2019 Jul 29.

Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan.

Microbiome studies estimate the functions of bacterial flora in situ on the basis of species composition and gene function; however, estimation of interspecies interaction networks is challenging. This study aimed to develop a method to predict the interaction networks among bacterial species from human gut metagenome data using bioinformatics methods. Our proposed method revealed that adjacent gene pairs involved in bacterial interspecies interactions are localized at boundary regions and encode membrane proteins mediating interactions between the intracellular and extracellular environments, e.g., transporters and channel proteins, and those mediating interactions between metabolic pathways. Actual human gut metagenome data displayed numerous such highly reliable interspecies interaction gene pairs in comparison with random simulated metagenome data sets, suggesting that the species composition of the actual microbiome facilitated more robust interspecific interactions. The present results indicate that molecular interaction networks in human gut flora are organized by a combination of interaction networks common to all individuals and group-specific interaction networks.
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http://dx.doi.org/10.1016/j.csbj.2019.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700418PMC
July 2019

Towards a standardized bioinformatics infrastructure for N- and O-glycomics.

Nat Commun 2019 07 22;10(1):3275. Epub 2019 Jul 22.

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden.

The mass spectrometry (MS)-based analysis of free polysaccharides and glycans released from proteins, lipids and proteoglycans increasingly relies on databases and software. Here, we review progress in the bioinformatics analysis of protein-released N- and O-linked glycans (N- and O-glycomics) and propose an e-infrastructure to overcome current deficits in data and experimental transparency. This workflow enables the standardized submission of MS-based glycomics information into the public repository UniCarb-DR. It implements the MIRAGE (Minimum Requirement for A Glycomics Experiment) reporting guidelines, storage of unprocessed MS data in the GlycoPOST repository and glycan structure registration using the GlyTouCan registry, thereby supporting the development and extension of a glycan structure knowledgebase.
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http://dx.doi.org/10.1038/s41467-019-11131-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796180PMC
July 2019
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