論文 - 冨田　勝

Meta-analysis of transcriptional regulatory networks for lipid metabolism in neural cells from schizophrenia patients based on an open-source intelligence approach.

Okamoto L, Watanabe S, Deno S, Nie X, Maruyama J, Tomita M, Hatano A, Yugi K

Neuroscience research （Neuroscience Research）  175   82 - 97 2021年12月

ISSN  0168-0102

　概要を見る

There have been a number of reports about the transcriptional regulatory networks in schizophrenia. However, most of these studies were based on a specific transcription factor or a single dataset, an approach that is inadequate to understand the diverse etiology and underlying common characteristics of schizophrenia. Here we reconstructed and compared the transcriptional regulatory network for lipid metabolism enzymes using 15 public transcriptome datasets of neural cells from schizophrenia patients. Since many of the well-known schizophrenia-related SNPs are in enhancers, we reconstructed a network including enhancer-dependent regulation and found that 53.3 % of the total number of edges (7,577 pairs) involved regulation via enhancers. By examining multiple datasets, we found common and unique transcriptional modes of regulation. Furthermore, enrichment analysis of SNPs that were connected with genes in the transcriptional regulatory networks by eQTL suggested an association with hematological cell counts and some other traits/diseases, whose relationship to schizophrenia was either not or insufficiently reported in previous studies. Based on these results, we suggest that in future studies on schizophrenia, information on genotype, comorbidities and hematological cell counts should be included, along with the transcriptome, for a more detailed genetic stratification and mechanistic exploration of schizophrenia.

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Decoding gut microbiota by imaging analysis of fecal samples.

Furusawa C, Tanabe K, Ishii C, Kagata N, Tomita M, Fukuda S

iScience （iScience）  24 （ 12 ） 103481 2021年12月

　概要を見る

The gut microbiota plays a crucial role in maintaining health. Monitoring the complex dynamics of its microbial population is, therefore, important. Here, we present a deep convolution network that can characterize the dynamic changes in the gut microbiota using low-resolution images of fecal samples. Further, we demonstrate that the microbial relative abundances, quantified via 16S rRNA amplicon sequencing, can be quantitatively predicted by the neural network. Our approach provides a simple and inexpensive method of gut microbiota analysis.

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Reliability of urinary charged metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry

Ishibashi Y., Harada S., Takeuchi A., Iida M., Kurihara A., Kato S., Kuwabara K., Hirata A., Shibuki T., Okamura T., Sugiyama D., Sato A., Amano K., Hirayama A., Sugimoto M., Soga T., Tomita M., Takebayashi T.

Scientific Reports 11 （ 1 ） 7407 2021年12月

　概要を見る

Currently, large-scale cohort studies for metabolome analysis have been launched globally. However, only a few studies have evaluated the reliability of urinary metabolome analysis. This study aimed to establish the reliability of urinary metabolomic profiling in cohort studies. In the Tsuruoka Metabolomics Cohort Study, 123 charged metabolites were identified and routinely quantified using capillary electrophoresis-mass spectrometry (CE-MS). We evaluated approximately 750 quality control (QC) samples and 6,720 participants’ spot urine samples. We calculated inter- and intra-batch coefficients of variation in the QC and participant samples and technical intraclass correlation coefficients (ICC). A correlation of metabolite concentrations between spot and 24-h urine samples obtained from 32 sub-cohort participants was also evaluated. The coefficient of variation (CV) was less than 20% for 87 metabolites (70.7%) and 20–30% for 19 metabolites (15.4%) in the QC samples. There was less than 20% inter-batch CV for 106 metabolites (86.2%). Most urinary metabolites would have reliability for measurement. The 96 metabolites (78.0%) was above 0.75 for the estimated ICC, and those might be useful for epidemiological analysis. Among individuals, the Pearson correlation coefficient of 24-h and spot urine was more than 70% for 59 of the 99 metabolites. These results show that the profiling of charged metabolites using CE-MS in morning spot human urine is suitable for epidemiological metabolomics studies.

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Reprogramming of glutamine metabolism via glutamine synthetase silencing induces cisplatin resistance in A2780 ovarian cancer cells

Guo J., Satoh K., Tabata S., Mori M., Tomita M., Soga T.

BMC Cancer 21 （ 1 ） 174 2021年12月

　概要を見る

Background: Cisplatin (CDDP) significantly prolongs survival in various cancers, but many patients also develop resistance that results in treatment failure. Thus, this study aimed to elucidate the underlying mechanisms by which ovarian cancer cells acquire CDDP resistance. Methods: We evaluated the metabolic profiles in CDDP-sensitive ovarian cancer A2780 cells and CDDP-resistant A2780cis cells using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). We further examined the expression of glutamine metabolism enzymes using real-time PCR and Western blot analyses. Cell viability was accessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The results showed that levels of glutamine, glutamate, and glutathione (GSH), a key drug resistance mediator synthesized from glutamate, were significantly elevated in A2780cis cells than those in A2780 cells. Furthermore, glutamine starvation decreased the GSH levels and CDDP resistance in A2780cis cells. Interestingly, the expression of glutamine synthetase (GS/GLUL), which synthesizes glutamine from glutamate and thereby negatively regulates GSH production, was almost completely suppressed in resistant A2780cis cells. In addition, treatment of A2780cis cells with 5-aza-2′-deoxycytidine, a DNA-demethylating agent, restored GS expression and reduced CDDP resistance. In contrast, GS knockdown in CDDP-sensitive A2780 cells induced CDDP resistance. Conclusions: The results indicate that upregulation of GSH synthesis from glutamine via DNA methylation-mediated silencing of GS causes CDDP resistance in A2780cis cells. Therefore, glutamine metabolism could be a novel therapeutic target against CDDP resistance.

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TGF-β-dependent reprogramming of amino acid metabolism induces epithelial–mesenchymal transition in non-small cell lung cancers

Nakasuka F., Tabata S., Sakamoto T., Hirayama A., Ebi H., Yamada T., Umetsu K., Ohishi M., Ueno A., Goto H., Sugimoto M., Nishioka Y., Yamada Y., Tomita M., Sasaki A.T., Yano S., Soga T.

Communications Biology 4 （ 1 ） 782 2021年12月

　概要を見る

Epithelial–mesenchymal transition (EMT)—a fundamental process in embryogenesis and wound healing—promotes tumor metastasis and resistance to chemotherapy. While studies have identified signaling components and transcriptional factors responsible in the TGF-β-dependent EMT, whether and how intracellular metabolism is integrated with EMT remains to be fully elucidated. Here, we showed that TGF-β induces reprogramming of intracellular amino acid metabolism, which is necessary to promote EMT in non-small cell lung cancer cells. Combined metabolome and transcriptome analysis identified prolyl 4-hydroxylase α3 (P4HA3), an enzyme implicated in cancer metabolism, to be upregulated during TGF-β stimulation. Further, knockdown of P4HA3 diminished TGF-β-dependent changes in amino acids, EMT, and tumor metastasis. Conversely, manipulation of extracellular amino acids induced EMT-like responses without TGF-β stimulation. These results suggest a previously unappreciated requirement for the reprogramming of amino acid metabolism via P4HA3 for TGF-β-dependent EMT and implicate a P4HA3 inhibitor as a potential therapeutic agent for cancer.

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Multiomics study of a heterotardigrade, Echinisicus testudo, suggests the possibility of convergent evolution of abundant heat-soluble proteins in Tardigrada.

Murai Y, Yagi-Utsumi M, Fujiwara M, Tanaka S, Tomita M, Kato K, Arakawa K

BMC genomics （BMC Genomics）  22 （ 1 ） 813 2021年11月

　概要を見る

Background: Many limno-terrestrial tardigrades can enter an ametabolic state, known as anhydrobiosis, upon desiccation, in which the animals can withstand extreme environments. Through genomics studies, molecular components of anhydrobiosis are beginning to be elucidated, such as the expansion of oxidative stress response genes, loss of stress signaling pathways, and gain of tardigrade-specific heat-soluble protein families designated CAHS and SAHS. However, to date, studies have predominantly investigated the class Eutardigrada, and molecular mechanisms in the remaining class, Heterotardigrada, still remains elusive. To address this gap in the research, we report a multiomics study of the heterotardigrade Echiniscus testudo, one of the most desiccation-tolerant species which is not yet culturable in laboratory conditions. Results: In order to elucidate the molecular basis of anhydrobiosis in E. testudo, we employed a multi-omics strategy encompassing genome sequencing, differential transcriptomics, and proteomics. Using ultra-low input library sequencing protocol from a single specimen, we sequenced and assembled the 153.7 Mbp genome annotated using RNA-Seq data. None of the previously identified tardigrade-specific abundant heat-soluble genes was conserved, while the loss and expansion of existing pathways were partly shared. Furthermore, we identified two families novel abundant heat-soluble proteins, which we named E. testudo Abundant Heat Soluble (EtAHS), that are predicted to contain large stretches of disordered regions. Likewise the AHS families in eutardigrada, EtAHS shows structural changes from random coil to alphahelix as the water content was decreased in vitro. These characteristics of EtAHS proteins are analogous to those of CAHS in eutardigrades, while there is no conservation at the sequence level. Conclusions: Our results suggest that Heterotardigrada have partly shared but distinct anhydrobiosis machinery compared with Eutardigrada, possibly due to convergent evolution within Tardigrada. (276/350).

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The evidence of temporary social parasitism by Polyrhachis lamellidens (Hymenoptera, Formicidae) in a Camponotus obscuripes colony (Hymenoptera, Formicidae)

Iwai H., Kurihara Y., Kono N., Tomita M., Arakawa K.

Insectes Sociaux （Insectes Sociaux）  68 （ 4 ） 375 - 382 2021年11月

ISSN  00201812

　概要を見る

Polyrhachis lamellidens is a temporary socially parasitic ant whose new queen utilizes other ant species in the early stages of colony foundation. Field observations and rearing experiments suggest that Camponotus japonicus is a host species of P. lamellidens. It is presumed that Camponotus obscuripes is also a host of P. lamellidens by rearing experiments and field observations; however, there are no records of P. lamellidens workers or brood coexisting in C. obscuripes colonies in field observations, and there is no clear evidence that C. obscuripes is a natural host of P. lamellidens. We conducted detailed field observations, behavioral tests, and rearing experiments to show that C. obscuripes is a host of temporary social parasites. We found colonies with P. lamellidens queens, workers, and larvae intermixed with C. obscuripes workers in the field. Behavioral tests showed that workers of both species in mixed colonies did not attack each other and maintained nestmate recognition ability, which suggests a collaborative nestmate relationship. Furthermore, a rearing experiment confirmed social parasitism by P. lamellidens among C. obscuripes by producing a mixed brood-producing colony. These are the first field and laboratory records of temporary social parasitism involving P. lamellidens and C. obscuripes.

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Urinary metabolome analyses of patients with acute kidney injury using capillary electrophoresis-mass spectrometry

Saito R., Hirayama A., Akiba A., Kamei Y., Kato Y., Ikeda S., Kwan B., Pu M., Natarajan L., Shinjo H., Akiyama S., Tomita M., Soga T., Maruyama S.

Metabolites （Metabolites）  11 （ 10 ）  2021年10月

ISSN  2218-1989

　概要を見る

Acute kidney injury (AKI) is defined as a rapid decline in kidney function. The associated syndromes may lead to increased morbidity and mortality, but its early detection remains difficult. Using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS), we analyzed the urinary metabolomic profile of patients admitted to the intensive care unit (ICU) after invasive surgery. Urine samples were collected at six time points: before surgery, at ICU admission and 6, 12, 24 and 48 h after. First, urine samples from 61 initial patients (non-AKI: 23, mild AKI: 24, severe AKI: 14) were measured, followed by the measurement of urine samples from 60 additional patients (non-AKI: 40, mild AKI: 20). Glycine and ethanolamine were decreased in patients with AKI compared with non-AKI patients at 6–24 h in the two groups. The linear statistical model constructed at each time point by machine learning achieved the best performance at 24 h (median AUC: 89%, cross-validated) for the 1st group. When cross-validated between the two groups, the AUC showed the best value of 70% at 12 h. These results identified metabolites and time points that show patterns specific to subjects who develop AKI, paving the way for the development of better biomarkers.

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Multicomponent nature underlies the extraordinary mechanical properties of spider dragline silk

Kono N., Nakamura H., Mori M., Yoshida Y., Ohtoshi R., Malay A.D., Pedrazzoli Moran D.A., Tomita M., Numata K., Arakawa K.

Proceedings of the National Academy of Sciences of the United States of America 118 （ 31 ）  2021年08月

ISSN  00278424

　概要を見る

Dragline silk of golden orb-weaver spiders (Nephilinae) is noted for its unsurpassed toughness, combining extraordinary extensibility and tensile strength, suggesting industrial application as a sustainable biopolymer material. To pinpoint the molecular composition of dragline silk and the roles of its constituents in achieving its mechanical properties, we report a multiomics approach, combining highquality genome sequencing and assembly, silk gland transcriptomics, and dragline silk proteomics of four Nephilinae spiders.We observed the consistent presence of the MaSp3B spidroin unique to this subfamily as well as several nonspidroin SpiCE proteins. Artificial synthesis and the combination of these components in vitro showed that the multicomponent nature of dragline silk, including MaSp3B and SpiCE, along with MaSp1 and MaSp2, is essential to realize the mechanical properties of spider dragline silk.

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RNA sequencing data for gamma radiation response in the extremotolerant tardigrade <i>Ramazzottius varieornatus</i>.

Yoshida Y, Horikawa DD, Sakashita T, Yokota Y, Kobayashi Y, Tomita M, Arakawa K

Data in brief 36   107111 2021年06月

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Quality assessment of untargeted analytical data in a large-scale metabolomic study

Saito R., Sugimoto M., Hirayama A., Soga T., Tomita M., Takebayashi T.

Journal of Clinical Medicine （Journal of Clinical Medicine）  10 （ 9 ）  2021年05月

ISSN  2077-0383

　概要を見る

Large-scale metabolomic studies have become common, and the reliability of the peak data produced by the various instruments is an important issue. However, less attention has been paid to the large number of uncharacterized peaks in untargeted metabolomics data. In this study, we tested various criteria to assess the reliability of 276 and 202 uncharacterized peaks that were detected in a gathered set of 30 plasma and urine quality control samples, respectively, using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). The linear relationship between the amounts of pooled samples and the corresponding peak areas was one of the criteria used to select reliable peaks. We used samples from approximately 3000 participants in the Tsuruoka Metabolome Cohort Study to investigate patterns of the areas of these uncharacterized peaks among the samples and clustered the peaks by combining the patterns and differences in the migration times. Our assessment pipeline removed substantial numbers of unreliable or redundant peaks and detected 35 and 74 reliable uncharacterized peaks in plasma and urine, respectively, some of which may correspond to metabolites involved in important physiological processes such as disease progression. We propose that our assessment pipeline can be used to help establish large-scale untargeted clinical metabolomic studies.

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A metabolomic profile predictive of new osteoporosis or sarcopenia development

Miyamoto K., Hirayama A., Sato Y., Ikeda S., Maruyama M., Soga T., Tomita M., Nakamura M., Matsumoto M., Yoshimura N., Miyamoto T.

Metabolites （Metabolites）  11 （ 5 ）  2021年05月

ISSN  2218-1989

　概要を見る

The increasing number of patients with osteoporosis and sarcopenia is a global concern among countries with progressively aging societies. The high medical costs of treating those patients suggest that prevention rather than treatment is preferable. We enrolled 729 subjects who attended both the second and third surveys of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study. Blood samples were collected from subjects at the second survey, and then a comprehensive metabolomic analysis was performed. It was found that 35 had newly developed osteoporosis at the third survey performed four years later, and 39 were newly diagnosed with sarcopenia at the third survey. In the second survey, we found that serum Gly levels were significantly higher even after adjustment for age, sex, and BMI in subjects with newly developed osteoporosis relative to those who remained osteoporosis-negative during the four-year follow-up. We also show that serum taurine levels were significantly lower at the second survey, even after adjustment for age, sex, and BMI in subjects with newly developed sarcopenia during the four-year follow-up compared with those not diagnosed with sarcopenia at the second or third surveys. Though our sample size and odds ratios were small, increased Gly and decreased taurine levels were found to be predictive of new development of osteoporosis and sarcopenia, respectively, within four years.

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Metabolomic analysis of small extracellular vesicles derived from pancreatic cancer cells cultured under normoxia and hypoxia

Hayasaka R., Tabata S., Hasebe M., Ikeda S., Ohnuma S., Mori M., Soga T., Tomita M., Hirayama A.

Metabolites （Metabolites）  11 （ 4 ）  2021年04月

ISSN  2218-1989

　概要を見る

Extracellular vesicles (EVs) released from cancer cells contribute to various malignant phenotypes of cancer, including metastasis, cachexia, and angiogenesis. Although DNA, mRNAs, miRNAs, and proteins contained in EVs have been extensively studied, the function of metabolites in EVs remains unclear. In this study, we performed a comprehensive metabolomic analysis of pancreatic cancer cells, PANC-1, cultured under different oxygen concentrations, and small EVs (sEVs) released from them, considering the fact that hypoxia contributes to the malignant behavior of cells in pancreatic cancer, which is a poorly diagnosed cancer. sEVs were collected by ultracen-trifugation, and hydrophilic metabolites were analyzed using capillary ion chromatography-mass spectrometry and liquid chromatography-mass spectrometry, and lipids were analyzed by supercrit-ical fluid chromatography-tandem mass spectrometry. A total of 140 hydrophilic metabolites and 494 lipids were detected in sEVs, and their profiles were different from those in cells. In addition, the metabolomic profile of sEVs was observed to change under hypoxic stress, and an increase in metabolites involved in angiogenesis was also detected. We reveal the hallmark of the metabolites contained in sEVs and the effect of tumor hypoxia on their profiles, which may help in understanding EV-mediated cancer malignancy.

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Xanthurenic acid is the main pigment of trichonephila clavata gold dragline silk

Fujiwara M., Kono N., Hirayama A., Malay A.D., Nakamura H., Ohtoshi R., Numata K., Tomita M., Arakawa K.

Biomolecules 11 （ 4 ）  2021年04月

　概要を見る

Spider silk is a natural fiber with remarkable strength, toughness, and elasticity that is attracting attention as a biomaterial of the future. Golden orb-weaving spiders (Trichonephila clavata) construct large, strong webs using golden threads. To characterize the pigment of golden T. clavata dragline silk, we used liquid chromatography and mass spectrometric analysis. We found that the major pigment in the golden dragline silk of T. clavata was xanthurenic acid. To investigate the possible function of the pigment, we tested the effect of xanthurenic acid on bacterial growth using gram-negative Escherichia coli and gram-positive Bacillus subtilis. We found that xanthurenic acid had a slight antibacterial effect. Furthermore, to investigate the UV tolerance of the T. clavata threads bleached of their golden color, we conducted tensile deformation tests and scanning electron microscope observations. However, in these experiments, no significant effect was observed. We therefore speculate that golden orb-weaving spiders use the pigment for other purposes, such as to attract their prey in the sunlight.

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Charged metabolite biomarkers of food intake assessed via plasma metabolomics in a population-based observational study in Japan

Shibutami E., Ishii R., Harada S., Kurihara A., Kuwabara K., Kato S., Iida M., Akiyama M., Sugiyama D., Hirayama A., Sato A., Amano K., Sugimoto M., Soga T., Tomita M., Takebayashi T.

PLoS ONE 16 （ 2 February ） e0246456 2021年02月

　概要を見る

Food intake biomarkers can be critical tools that can be used to objectively assess dietary exposure for both epidemiological and clinical nutrition studies. While an accurate estimation of food intake is essential to unravel associations between the intake and specific health conditions, random and systematic errors affect self-reported assessments. This study aimed to clarify how habitual food intake influences the circulating plasma metabolome in a free-living Japanese regional population and to identify potential food intake biomarkers. To achieve this aim, we conducted a cross-sectional analysis as part of a large cohort study. From a baseline survey of the Tsuruoka Metabolome Cohort Study, 7, 012 eligible male and female participants aged 40-69 years were chosen for this study. All data on patients' health status and dietary intake were assessed via a food frequency questionnaire, and plasma samples were obtained during an annual physical examination. Ninety-four charged plasma metabolites were measured using capillary electrophoresis mass spectrometry, by a non-targeted approach. Statistical analysis was performed using partial-least-square regression. A total of 21 plasma metabolites were likely to be associated with long-term food intake of nine food groups. In particular, the influential compounds in each food group were hydroxyproline for meat, trimethylamine- N-oxide for fish, choline for eggs, galactarate for dairy, cystine and betaine for soy products, threonate and galactarate for carotenoid-rich vegetables, proline betaine for fruits, quinate and trigonelline for coffee, and pipecolate for alcohol, and these were considered as prominent food intake markers in Japanese eating habits. A set of circulating plasma metabolites was identified as potential food intake biomarkers in the Japanese community-dwelling population. These results will open the way for the application of new reliable dietary assessment tools not by self-reported measurements but through objective quantification of biofluids.

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Quantitative and Molecular Similarity Analyses of the Metabolites of Cold- A nd Hot-Natured Chinese Herbs

Guo J., Wang J., Iino K., Tomita M., Soga T.

Evidence-based Complementary and Alternative Medicine 2021   6646507 2021年

ISSN  1741427X

　概要を見る

Background. Based on the theory of traditional Chinese medicine, Chinese herbs possess four different medicinal properties: Hot, warm, cold, and cool. These serve as a reference guide for these herbal medicines. However, the molecular mechanisms supporting their relevance remain unclear. Methods. We performed metabolomics based on capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS) and multivariate data analysis for the structural identification of compounds of cold- A nd hot-natured Chinese herbs. Results. To this end, 30 selected herbs were analyzed and a total of 416 metabolites were identified via CE-TOF/MS, of which 193 compounds were detected in most herbs. The observed profiles offered the potential to understand the mechanism of association between the compounds and nature of the Chinese herbs. Comparison of the similarity in terms of chemical and molecular structures and content revealed that hot-natured herbs contained more nucleotides. In contrast, principal component analysis revealed the presence of more amino acid compounds in cold-natured herbs. Conclusion. Comparing the structural similarities between the samples using the Tanimoto coefficient revealed that a general non-specific structure was observed between cold- A nd hot-natured herbs; however, the distribution of the molecular groups seemed to contribute more toward the energy properties.

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Upregulation of Thymidylate Synthase Induces Pemetrexed Resistance in Malignant Pleural Mesothelioma.

Sato Y, Tomita M, Soga T, Ochiai A, Makinoshima H

Frontiers in pharmacology （Frontiers in Pharmacology）  12   718675 2021年

ISSN  1663-9812

　概要を見る

Malignant pleural mesothelioma (MPM) is an invasive malignancy that develops in the pleural cavity, and antifolates are used as chemotherapeutics for treating. The majority of antifolates, including pemetrexed (PMX), inhibit enzymes involved in purine and pyrimidine synthesis. MPM patients frequently develop drug resistance in clinical practice, however the associated drug-resistance mechanism is not well understood. This study was aimed to elucidate the mechanism underlying resistance to PMX in MPM cell lines. We found that among the differentially expressed genes associated with drug resistance (determined by RNA sequencing), TYMS expression was higher in the established resistant cell lines than in the parental cell lines. Knocking down TYMS expression significantly reduced drug resistance in the resistant cell lines. Conversely, TYMS overexpression significantly increased drug resistance in the parental cells. Metabolomics analysis revealed that the levels of dTMP were higher in the resistant cell lines than in the parental cell lines; however, resistant cells showed no changes in dTTP levels after PMX treatment. We found that the nucleic acid-biosynthetic pathway is important for predicting the efficacy of PMX in MPM cells. The results of chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assays suggested that H3K27 acetylation in the 5′-UTR of TYMS may promote its expression in drug-resistant cells. Our findings indicate that the intracellular levels of dTMP are potential biomarkers for the effective treatment of patients with MPM and suggest the importance of regulatory mechanisms of TYMS expression in the disease.

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Correlation-centred variable selection of a gene expression signature to predict breast cancer metastasis

Hikichi S., Sugimoto M., Tomita M.

Scientific Reports （Scientific Reports）  10 （ 1 ） 7923 2020年12月

　概要を見る

Predictions of distant cancer metastasis based on gene signatures are studied intensively to realise precise diagnosis and treatments. Gene selection i.e. feature selection is a cornerstone to both establish accurate predictions and understand underlying pathologies. Here, we developed a simple but robust feature selection method using a correlation-centred approach to select minimal gene sets that have both high predictive and generalisation abilities. A multiple logistic regression model was used to predict 5-year metastases of patients with breast cancer. Gene expression data obtained from tumour samples of lymph node-negative breast cancer patients were randomly split into training and validation data. Our method selected 12 genes using training data and this showed a higher area under the receiver operating characteristic curve of 0.730 compared with 0.579 yielded by previously reported 76 genes. The signature with the predictive model was validated in an independent dataset, and its higher generalization ability was observed. Gene ontology analyses revealed that our method consistently selected genes with identical functions which frequently selected by the 76 genes. Taken together, our method identifies fewer gene sets bearing high predictive abilities, which would be versatile and applicable to predict other factors such as the outcomes of medical treatments and prognoses of other cancer types.

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Spidroin profiling of cribellate spiders provides insight into the evolution of spider prey capture strategies

Kono N., Nakamura H., Mori M., Tomita M., Arakawa K.

Scientific Reports （Scientific Reports）  10 （ 1 ） 15721 2020年12月

　概要を見る

Orb-weaving spiders have two main methods of prey capture: cribellate spiders use dry, sticky capture threads, and ecribellate spiders use viscid glue droplets. Predation behaviour is a major evolutionary driving force, and it is important on spider phylogeny whether the cribellate and ecribellate spiders each evolved the orb architecture independently or both strategies were derived from an ancient orb web. These hypotheses have been discussed based on behavioural and morphological characteristics, with little discussion on this subject from the perspective of molecular materials of orb web, since there is little information about cribellate spider-associated spidroin genes. Here, we present in detail a spidroin catalogue of six uloborid species of cribellate orb-weaving spiders, including cribellate and pseudoflagelliform spidroins, with transcriptome assembly complemented with long read sequencing, where silk composition is confirmed by proteomics. Comparative analysis across families (Araneidae and Uloboridae) shows that the gene architecture, repetitive domains, and amino acid frequencies of the orb web constituting silk proteins are similar among orb-weaving spiders regardless of the prey capture strategy. Notably, the fact that there is a difference only in the prey capture thread proteins strongly supports the monophyletic origin of the orb web.

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Integrated omics profiling of dextran sodium sulfate-induced colitic mice supplemented with Wolfberry (Lycium barbarum)

Aw W., Jia H., Lyu W., Fukuda S., Tomita M., Otani L., Kato H.

npj Science of Food （npj Science of Food）  4 （ 1 ） 5 2020年12月

　概要を見る

We used a multi-omics profiling approach to investigate the suppressive effects of 2% Wolfberry (WOL)-enriched diets on dextran sodium sulfate (DSS)-induced colitis in mice. It was observed that in mice fed the WOL diet, the disease activity index, colon shortening, plasma concentrations of matrix metalloproteinase-3 and relative mesenteric fat weight were significantly improved as compared to the DSS group. Results from colon transcriptome and proteome profiles showed that WOL supplementation significantly ameliorated the expression of genes and proteins associated with the integrity of the colonic mucosal wall and colonic inflammation. Based on the hepatic transcriptome, proteome and metabolome data, genes involved in fatty acid metabolism, proteins involved in inflammation and metabolites related to glycolysis were downregulated in WOL mice, leading to lowered inflammation and changes in these molecules may have led to improvement in body weight loss. The integrated nutrigenomic approach thus revealed the molecular mechanisms underlying the ameliorative effect of whole WOL fruit consumption on inflammatory bowel disease.

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