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NURECON: A Novel Online System for Determining Nutrition Requirements Based on Microbial Composition

IEEE/ACM Transactions on Computational Biology and bioinformatics 2024年第2期21卷 254-264页

作者： Hu, Zhao-Qi Hung, Yuan-Mao Chen, Li-Han Lai, Liang-Chuan Pan, Min-Hsiung Chuang, Eric Y. Tsai, Mong-Hsun National Taiwan University Institute of Biotechnology Graduate Institute of Biomedical Electronics and Bioinformatics Taipei10617 Taiwan National Taiwan University Graduate Institute of Biomedical Electronics and Bioinformatics Taipei10617 Taiwan National Taiwan University Institute of Fisheries Science Department of Life Science Taipei10617 Taiwan National Taiwan University Graduate Institute of Physiology College of Medicine and Bioinformatics and Biostatistics Core Center of Genomic and Precision Medicine Taipei10617 Taiwan National Taiwan University Institute of Food Sciences and Technology Taipei10617 Taiwan National Taiwan University Grad. Inst. of Biomedical Electronics and Bioinformatics and Bioinformatics and Biostatistics Core Center of Genomic and Precision Medicine Taipei10617 Taiwan Industrial Technology Research Institute Biomedical Technology and Device Research Laboratories Hsinchu310401 Taiwan National Taiwan University Institute of Biotechnology Taipei10617 Taiwan

Dietary habits have been proven to have an impact on the microbial composition and health of the human gut. Over the past decade, researchers have discovered that gut microbiota can use nutrients to produce metabolites that have major implications for human physiology. However, there is no comprehensive system that specifically focuses on identifying nutrient deficiencies based on gut microbiota, making it difficult to interpret and compare gut microbiome data in the literature. This study proposes an analytical platform, NURECON, that can predict nutrient deficiency information in individuals by comparing their metagenomic information to a reference baseline. NURECON integrates a next-generation bacterial 16S rRNA analytical pipeline (QIIME2), metabolic pathway prediction tools (PICRUSt2 and KEGG), and a food compound database (FooDB) to enable the identification of missing nutrients and provide personalized dietary suggestions. Metagenomic information from total number of 287 healthy subjects was used to establish baseline microbial composition and metabolic profiles. The uploaded data is analyzed and compared to the baseline for nutrient deficiency assessment. Visualization results include gut microbial composition, related enzymes, pathways, and nutrient abundance. NURECON is a user-friendly online platform that provides nutritional advice to support dietitians' research or menu design. © 2004-2012 IEEE.

关键词： Enzymes

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Controllability and stability analysis of large transcriptomic dynamic systems for host response to influenza infection in human

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Infectious Disease Modelling 2016年第1期1卷 52-70页

作者： Xiaodian Sun Fang Hu Shuang Wu Xing Qiu Patrice Linel Hulin Wu Biostatistics and Bioinformatics Core Sylvester Comprehensive Cancer CenterUniversity of MiamiMiamiUSA Department of Biostatistics and Computational Biology University of Rochester School of Medicine and DentistryRochesterNYUSA Genus PLC ABS GlobalDeforestWIUSA Department of Biostatistics School of Public HealthUniversity of Texas Health Science Center at HoustonHoustonTXUSA

Background:Gene regulatory networks are complex dynamic systems and the reverseengineering of such networks from high-dimensional time course transcriptomic data have attracted researchers from various *** is also interesting and important to study the behavior of the reconstructed networks on the basis of dynamic models and the biological *** focus on the gene regulatory networks reconstructed using the ordinary differential equation(ODE)modelling approach and investigate the properties of these ***:Controllability and stability analyses are conducted for the reconstructed gene response networks of 17 influenza infected subjects based on ODE *** subjects tend to have larger numbers of driver nodes,higher proportions of critical links and lower proportions of redundant links than asymptomatic *** also show that the degree distribution,rather than the structure of networks,plays an important role in controlling the network in response to influenza *** addition,we find that the stability of high-dimensional networks is very sensitive to randomness in the reconstructed systems brought by errors in measurements and parameter ***:The gene response networks of asymptomatic subjects are easier to be controlled than those of symptomatic *** may indicate that the regulatory systems of asymptomatic subjects are easier to recover from disease stimulations,so these subjects are less likely to develop *** results also suggest that stability constraint should be considered in the modelling of high-dimensional networks and the estimation of network parameters.

关键词： network stability networks

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Methylscaper: an R/Shiny app for joint visualization of DNA methylation and nucleosome occupancy in single-molecule and single-cell data

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bioinformatics 2021年第24期37卷 4857-4859页

作者： Knight, Parker Gauthier, Marie-Pierre L. Pardo, Carolina E. Darst, Russell P. Kapadia, Kevin Browder, Hadley Morton, Eliza Riva, Alberto Kladde, Michael P. Bacher, Rhonda Department of Biostatistics University of Florida Gainesville FL USA Department of Biochemistry and Molecular Biology University of Florida Gainesville FL USA Department of Statistics University of Florida Gainesville FL USA Bioinformatics Core Interdisciplinary Center for Biotechnology Research University of Florida Gainesville FL USA

A Summary: Differential DNA methylation and chromatin accessibility are associated with disease development, particularly cancer. Methods that allow profiling of these epigenetic mechanisms in the same reaction and at the single-molecule or single-cell level continue to emerge. However, a challenge lies in jointly visualizing and analyzing the heterogeneous nature of the data and extracting regulatory insight. Here, we present methylscaper, a visualization framework for simultaneous analysis of DNA methylation and chromatin accessibility landscapes. Methylscaper implements a weighted principal component analysis that orders DNA molecules, each providing a record of the chromatin state of one epiallele, and reveals patterns of nucleosome positioning, transcription factor occupancy, and DNA methylation. We demonstrate methylscaper's utility on a long-read, single-molecule methyltransferase accessibility protocol for individual templates (MAPit-BGS) dataset and a single-cell nucleosome, methylation, and transcription sequencing (scNMT-seq) dataset. In comparison to other procedures, methylscaper is able to readily identify chromatin features that are biologically relevant to transcriptional status while scaling to larger datasets.

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Combining Comparative Genomics with de novo Motif Discovery to Identify Human Transcription Factor DNA-Binding Motifs

Combining Comparative Genomics with de novo Motif Discovery ...

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International Multi-Symposiums on Computer and Computational Sciences (IMSCCS)

作者： Linyong Mao W Jim Zheng Department of Biostatistics Bioinformatics and Epidemiology and Bioinformatics Core Facility Hollings Cancer Center Medical University of South Carolina Charleston SC USA

As more and more genomes are sequenced, comparative genomics approaches provide a methodology for identifying conserved regulatory elements that may be involved in gene regulation. In this study, we combined comparative genomics with de novo motif discovery to identify potential human transcription factor binding motifs that are overrepresented and conserved in the upstream regions of a set of co-regulated genes. We validated our approach by analyzing a well-characterized muscle specific gene set. Our approach also performed better than other existing programs, such as Toucan and Compare Prospector, based on the motif discovery results for the muscle data set

关键词： Genomics bioinformatics Humans Muscles Sequences DNA Mice Sampling methods Cancer Heuristic algorithms

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Antibody-secreting cell repertoires hold high-affinity anti-rocuronium specificities that can induce anaphylaxis in vivo

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Journal of Allergy and Clinical Immunology 2025年第5期155卷 1557-1574页

作者： Dejoux, Alice Zhu, Qianqian Woolfe, Adam Godon, Ophélie Ellouze, Sami Mottet, Guillaume Castrillon, Carlos Gillis, Caitlin Pecalvel, Cyprien Ganneau, Christelle Iannascoli, Bruno Lemoine, Frédéric Saul, Frederick England, Patrick Reber, Laurent L. Gouel-Chéron, Aurélie de Chaisemartin, Luc Haouz, Ahmed Millot, Gaël A. Bay, Sylvie Gérard, Annabelle Jönsson, Friederike Chollet-Martin, Sylvie Bruhns, Pierre Institut Pasteur Université Paris Cité Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1222 Antibodies in Therapy and Pathology Paris France Collège Doctoral Sorbonne Université Paris France Université Paris-Saclay INSERM Inflammation Microbiome Immunosurveillance Orsay France HiFiBiO Therapeutics SAS Paris France Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291 Centre National de la Recherche Scientifique (CNRS) UMR5051 University Toulouse III Toulouse France Institut Pasteur Université Paris Cité CNRS UMR3523 Chimie des Biomolécules Paris France Institut Pasteur Université Paris Cité Bioinformatics and Biostatistics Hub Paris France Institut Pasteur Université Paris Cité CNRS UMR3528 Plate-forme Cristallographie-C2RT Paris France Institut Pasteur Université Paris Cité CNRS UMR3528 Molecular Biophysics Core Facility Paris France Anaesthesiology and Critical Care Medicine Department DMU Parabol Bichat-Claude Bernard Hospital Assistance Publique-Hôpitaux de Paris Paris France Université Paris Cité Paris France Service d'immunologie Hôpital Bichat Assistance Publique Hôpitaux de Paris Paris France CNRS F-75015 Paris France INSERM 1152 Département Hospitalo-Universitaire FIRE Labex Inflamex Université Paris Diderot Paris France

Background: Neuromuscular blocking agents (NMBAs) are muscle relaxants used to assist mechanical ventilation but lead in 1 per 10,000 anesthesia cases to severe acute hypersensitivity reactions—that is, anaphylaxis. Incidences vary between types of NMBAs. Rocuronium, a widely used nondepolarizing aminosteroid NMBA, induces among the highest anaphylaxis rates. Rocuronium-induced anaphylaxis is proposed to rely on preexisting rocuronium-binding antibodies, but no such antibodies have ever been identified. Objectives: We sought to identify rocuronium-specific antibody repertoires from plasma cells or plasmablasts of rocuronium-immunized mice to determine the affinities, structures, and anaphylactogenic potential of these antibodies for rocuronium. Methods: We engrafted rocuronium onto carrier proteins allowing immunization of mice against rocuronium, screening for rocuronium-specific antibody responses, and sorting of rocuronium-specific plasma cells using droplet microfluids coupled to single-cell antibody gene (variable heavy chain [VH] and variable light chain [VL]) sequencing. Results: The 2 different repertoires of >500 VH-VL pairs were oligoclonal, comprised 3 major clonal families, and displayed convergence. Expressed as human IgG1, these antibodies demonstrated subnanomolar affinities for rocuronium with families either monospecific for rocuronium or cross-reactive only for closely related NMBAs. Expressed as human IgE, they triggered human mast cell and basophil activation, and severe passive systemic anaphylaxis in mice humanized for the IgE receptor FcεRI. Cocrystal structures between rocuronium and antibody representatives of 3 different VH-VL families revealed distinct interaction modes, with the ammonium group involved systematically in the binding interface. Conclusions: This work identifies the epitopes of antibody reactivity to rocuronium, demonstrates anaphylactogenic potential of anti-rocuronium IgE, and establishes the first mouse model of NMBA anap

关键词： allergy anaphylaxis Antibodies B cells neuromuscular blocking agents plasma cells rocuronium therapy

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Restoration of LAT activity improves CAR T cell sensitivity and persistence in response to antigen-low acute lymphoblastic leukemia

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Cancer Cell 2025年第3期43卷 482-502.e9页

作者： Pham-Danis, Catherine Novak, Amanda J. Danis, Etienne McClellan, Samantha M. Leach, Lillie Yarnell, Michael C. Ebmeier, Christopher C. Tasian, Sarah K. Kohler, M. Eric Department of Pediatrics University of Colorado Anschutz Medical Campus Aurora 80045 CO United States Department of Biomedical Informatics University of Colorado Anschutz Medical Campus Aurora 80045 CO United States Biostatistics & Bioinformatics Shared Resource University of Colorado Cancer Center Aurora 80045 CO United States Division of Oncology and Center for Childhood Cancer Research Children's Hospital of Philadelphia Philadelphia 19104 PA United States Proteomics and Mass Spectrometry Core Department of Biochemistry University of Colorado Boulder 80309 CO United States Department of Pediatrics & Abramson Cancer Center University of Pennsylvania Perelman School of Medicine Philadelphia 19104 PA United States Division of Blood and Marrow Transplantation & Cellular Therapy Center for Cancer and Blood Disorders Children's Hospital Colorado Aurora 80045 CO United States

Chimeric antigen receptor (CAR) T cells induce responses in patients with relapsed/refractory leukemia;however, long-term efficacy is frequently limited by relapse. The inability to target antigen-low cells is an intrinsic vulnerability of second-generation CAR T cells and underlies most relapses following CD22BBz CAR T cell therapy. Here, we interrogate CD22BBz CAR signaling in response to low antigen and find inefficient phosphorylation of the linker for activation of T cells (LAT) limiting downstream signaling. To overcome this, we designed the adjunctive LAT-activating CAR T cell (ALA-CART) platform, pairing a second-generation CAR with a LAT-CAR incorporating the intracellular domain of LAT. ALA-CART cells demonstrate reduced differentiation during manufacturing and increased LAT phosphorylation, MAPK signaling, and AP-1 activity. ALA-CART cells show improved cytotoxicity, proliferation, persistence, and efficacy against antigen-low leukemias that were refractory to clinically active CD22BBz CAR T cells. Restoration of LAT signaling through the ALA-CART platform represents a promising strategy for overcoming multiple mechanisms of CAR T cell failure. © 2025 The Authors

关键词： ALL CAR T cells immunotherapy LAT T cell signaling

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The relationship of cervical microbiota diversity with race and disparities in preterm birth

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Journal of Neonatal-Perinatal Medicine 2018年第3期11卷 231-239页

作者： Wheeler, Sarahn Pryor, Katherine Antczak, Brian Truong, Tracy Murtha, Amy Seed, Patrick Department of Obstetrics and Gynecology Division of Maternal Fetal Medicine Duke University School of Medicine DUMC Box 3967 Durham NC United States Department of Biostatistics and Bioinformatics Biostatistics Core Duke University School of Medicine Durham NC United States Department of Pediatrics Division of Infectious Diseases Northwestern Feinberg School of Medicine Chicago IL United States

OBJECTIVE: Pregnant non-Hispanic blacks (NHB) have increased vaginal microbiome diversity compared to non-Hispanic whites (NHW) which may contribute to increased preterm birth. Cervical microbiome diversity is poorly characterized in pregnancy, therefore our objective was to correlate cervical microbiota diversity with cervico-vaginal inflammation by race and delivery timing. STUDY DESIGN: Pregnant women were recruited in the first and second trimesters. A sterile cervical swab and saline lavage were collected at a single time point. Using 16S rRNA sequencing, Chao1 and Shannon Diversity (SDI) indicies were measured and compared by race and delivery timing (preterm *** delivery). Cervico-vaginal inflammatory markers were also compared by race and delivery timing. Spearman correlation coefficients between cervical microbiome diversity and cervico-vaginal inflammatory markers were calculated. RESULTS: Of the 51 subjects, 39 (76%) were NHB and 12 (24%) were NHW. Cervical microbiota SDI was significantly higher in NHB compared to NHW (0.5 vs. 0.1;p = 0.03). However, there were no difference in Chao1 diversity or cervico-vaginal inflammatory markers by race or delivery timing. CONCLUSION: Our findings suggest the cervical microbiota diversity during pregnancy differs by race. Larger cohort studies will further determine if altered cervical diversity is part of the pathogenesis of PTB and explains race disparities. © © 2018-IOS Press and the authors. All rights reserved.

关键词： disparities Microbiome preterm birth race

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Modeling competing endogenous RNA regulatory networks in glioblastoma multiforme

Modeling competing endogenous RNA regulatory networks in gli...

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IEEE International Conference on bioinformatics and Biomedicine (BIBM)

作者： Yu-Chiao Chiu Eric Y. Chuang Tzu-Hung Hsiao Yidong Chen Graduate Institute of Biomedical Electronics and Bioinformatics Bioinformatics and Biostatistics Core National Taiwan University Taipei Taiwan Greehey Children's Cancer Research Institute

Recent studies postulated that genes harboring identical microRNA (miRNA) binding sites can crosstalk by competing for a limited pool of the binding miRNAs (the miRNA program), named as the regulation of competing endogenous RNAs (ceRNAs). Incorporating recent biological evidence that ceRNA regulation depends on miRNA program expression levels, we developed, in the present study, a mathematical model for systematically inferring ceRNA regulation that is dependent on expression levels of the miRNA programs from sample-paired mRNA and miRNA expression datasets. Applying the method to analyze glioblastoma datasets, a compact ceRNA regulatory network was constructed. Our data further demonstrated that ceRNA regulation plays an essential role in transient cellular responses to dynamic inter-cellular signals. The findings illuminate mechanism of ceRNA regulation and further provide biological insights into the complex human interactome.

关键词： bioinformatics Correlation coefficient RNA Genomics Gene expression Cancer

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Characterization of conditions for competing endogenous RNA regulation in GBM

Characterization of conditions for competing endogenous RNA ...

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IEEE International Workshop on Genomic Signal Processing and Statistics (GENSIPS)

Summary form only given. MicroRNAs (miRNAs) are short non-coding RNAs with the average length of 22 nucleotides. They are known to induce mRNA degradation or suppression of translation by complementarily binding to 3' untranslated regions (3' UTRs) of target mRNA transcripts. Recently, an alternative mechanism through which miRNAs participate in gene regulation was postulated and experimentally validated, namely the competing endogenous RNAs (ceRNAs). By competing for a limited pool of common targeting miRNAs (miRNA programs; miRP), pairs of genes (ceRNAs) sharing, fully or partially, identical miRNAs binding sites can “talk” to each other: when one ceRNA is up-regulated (or down-regulated) in cells, it attracts (or releases) the targeting miRNAs away from (or toward) the other ceRNA, and in turn have protective (or harmful) effects on expression of the other ceRNA. Based on in silico and in vitro analysis, recent reports suggested the dynamic and condition-specific properties of ceRNA regulation. The essential factors involved in ceRNA regulation include size of miRP, number of miRP binding sites, expression level of miRP, and expression level of ceRNAs. For better characterizing the optimal conditions for ceRNA regulation, in the present study we aim to confer how essential factors determine strength of ceRNA regulation in vivo, by analyzing TCGA datasets of glioblastoma multiforme (GBM) patients with 491 tumor samples profiled with paired miRNA and gene expression. Based on the definition that two genes sharing any number of common targeting miRNAs as a putative ceRNA pair, and by utilizing TargetScan algorithm, we identified 47,451,423 putative ceRNA pairs, involving 10,872 ceRNAs (genes). Pairwise correlation coefficients of gene expression profiles were then computed for each of the putative ceRNA pairs, and then the CDF. Varying size of miRP, for example, generated multiple CDFs, and then the goodness-of-fit was performed for pinpointing the essential factors

关键词： RNA bioinformatics Educational institutions In vivo Gene expression Biomedical electronics Pediatrics

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Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in Lrp5

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Bone Research 2023年第3期11卷 595-606页

作者： Cassandra R.Diegel Ina Kramer Charles Moes Gabrielle E.Foxa Mitchell J.McDonald Zachary B.Madaj Sabine Guth Jun Liu Jennifer L.Harris Michaela Kneissel Bart O.Williams Department of Cell Biology Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA Diseases of Aging and Regenerative Medicine Novartis Institutes for Biomedical ResearchCH-4002 BaselSwitzerland Bioinformatics and Biostatistics Core Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA Oncology Novartis Institutes for Biomedical ResearchSan DiegoCA 92121USA

Proper regulation of Wnt signaling is critical for normal bone development and *** in several Wnt signaling components,which increase the activity of the pathway in the skeleton,cause high bone mass in human subjects and mouse *** bone mass is often accompanied by severe headaches from increased intracranial pressure,which can lead to fatality and loss of vision or hearing due to the entrapment of cranial *** addition,progressive forehead bossing and mandibular overgrowth occur in almost all *** that would provide symptomatic relief in these subjects are ***-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled *** inhibition of porcupine is a highly selective method of Wnt signaling *** treated three different mouse models of high bone mass caused by aberrant Wnt signaling,including homozygosity for loss-of-function in Sost,which models sclerosteosis,and two strains of mice carrying different point mutations in Lrp5(equivalent to human G171V and A214V),at 3 months of age with porcupine inhibitors for 5–6 *** significantly reduced both trabecular and cortical bone mass in all three *** demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.

关键词： homeostasis function mass

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