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arXiv 2023年

作者： Despotovic, Vladimir Kim, Sang-Yoon Hau, Ann-Christin Kakoichankava, Aliaksandra Klamminger, Gilbert Georg Borgmann, Felix Bruno Kleine Frauenknecht, Katrin B.M. Mittelbronn, Michel Nazarov, Petr V. Bioinformatics Platform Data Integration and Analysis Unit Luxembourg Institute of Health Strassen Luxembourg Dr. Senckenberg Institute of Neurooncology University Hospital Frankfurt Frankfurt am Main Germany Edinger Institute Institute of Neurology Goethe University Frankfurt am Main Germany Frankfurt Cancer Institute Goethe University Frankfurt am Main Germany University Cancer Center Frankfurt Frankfurt am Main Germany University Hospital Goethe University Frankfurt am Main Germany Laboratoire national de santé National Center of Pathology Dudelange Luxembourg Multi-Omics Data Science group Department of Cancer Research Luxembourg Institute of Health Strassen Luxembourg Luxembourg Centre of Neuropathology Dudelange Luxembourg Klinik für Frauenheilkunde Geburtshilfe und Reproduktionsmedizin Saarland University Homburg Germany Department of Cancer Research Luxembourg Institute of Health Strassen Luxembourg Luxembourg Centre for Systems Biomedicine University of Luxembourg Belval Luxembourg Department of Life Sciences and Medicine University of Luxembourg Esch-sur-Alzette Luxembourg Faculty of Science Technology and Medicine University of Luxembourg Esch-sur-Alzette Luxembourg

We provide in this paper a comprehensive comparison of various transfer learning strategies and deep learning architectures for computer-aided classification of adult-type diffuse gliomas. We evaluate the generalizability of out-of-domain ImageNet representations for a target domain of histopathological images, and study the impact of in-domain adaptation using self-supervised and multi-task learning approaches for pretraining the models using the medium-to-large scale datasets of histopathological images. A semi-supervised learning approach is furthermore proposed, where the fine-tuned models are utilized to predict the labels of unannotated regions of the whole slide images (WSI). The models are subsequently retrained using the ground-truth labels and weak labels determined in the previous step, providing superior performance in comparison to standard in-domain transfer learning with balanced accuracy of 96.91% and F1-score 97.07%, and minimizing the pathologist’s efforts for annotation. Finally, we provide a visualization tool working at WSI level which generates heatmaps that highlight tumor areas;thus, providing insights to pathologists concerning the most informative parts of the WSI. © 2023, CC BY-NC-ND.

关键词： Tumors

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Genome-Wide Association Study of Intraocular Pressure in Population-Based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study

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Ophthalmology science 2025年第5期5卷

作者： Nobuo Fuse Hayato Anzawa Miyuki Sakurai Ikuko N. Motoike Satoshi Nagaie Tomohiro Nakamura Akiko Miyazawa Eiichi N. Kodama Masatsugu Orui Yohei Hamanaka Tomoko Kobayashi Akira Uruno Makiko Taira Ritsuko Shimizu Naoki Nakaya Mami Ishikuro Taku Obara Fuji Nagami Soichi Ogishima Fumiki Katsuoka Masayuki Yamamoto Tohoku Medical Megabank Organization Tohoku University Sendai Japan Department of System Bioinformatics Tohoku University Graduate School of Information Sciences Sendai Japan Department of Data Science Kyoto Women's University Kyoto Japan Tohoku University International Research Institute of Disaster Science Sendai Japan Tohoku University Graduate School of Medicine Sendai Japan Advanced Research Center for Innovations in Next-Generation Medicine Tohoku University Sendai Japan

Purpose This study was conducted to elucidate the distribution and determinants of ocular biometric parameters and to assess the association between intraocular pressure (IOP) and single nucleotide polymorphisms (SNPs) in the Japanese population–based genome cohort studies. Design Cross-sectional analysis involving genome-wide association studies (GWASs). Participants In total, 22 150 participants aged >18 years from the population cohort (Community-Based Cohort [CommCohort]) and 11 302 participants from the Birth and Three-Generation (BirThree) Cohort of the Tohoku Medical Megabank Organization Eye Study were examined. Methods Participant underwent interviews, ophthalmic and physiological examinations, laboratory tests, and microarray analyses. Genome-wide association studies were conducted in the CommCohort (discovery stage) and the BirThree Cohort (replication stage), followed by a meta-analysis. Associations of SNPs and IOP were evaluated using a genome-wide significance threshold (5 × 10 − 8 ). Main Outcome Measures Association of SNPs with IOP and distributions of IOP by sex and age. Results In the discovery stage, the mean IOP of the right and left eye was 13.95 and 14.02 mmHg, respectively. In the replication stage, the corresponding values were 14.32 and 14.27 mmHg, respectively. A significant age-related reduction in IOP was observed in both stages ( P < 0.001). Genome-wide association studies identified 573 and 2 genome-wide significant SNPs in the discovery and replication stages, respectively. Meta-analysis revealed 1601 significant SNPs across 21 loci on 11 chromosomes (Chrs). Of these loci, 17 were previously known to be associated with IOP or glaucoma, while four—septin-8 ( SEPT8 ; Chr5), aldehyde dehydrogenase 2 ( ALDH2 ; Chr12), collagen type VI alpha 2 chain ( COL6A2 ; Chr21), and Wnt family member 7B ( WNT7B ; Chr22)—were newly identified. Conclusions This large-scale GWAS in a Japanese population identified 21 loci associated with IOP, including

关键词： Intraocular pressure Population-based cohort study Genome-wide association study (GWAS) AL axial length ALDH2 aldehyde dehydrogenase 2 ANAPC1 anaphase promoting complex subunit 1 ARHGEF12 Rho Guanine Nucleotide Exchange Factor 12 ABCA1 ATP binding cassette subfamily A member 1 BirThree Birth and Three-Generation CAMTA2 calmodulin binding transcription activator 2 CAV caveolin CCT central corneal thickness CDKN2B-AS1 CDKN2B and CDKN2A antisense cis and trans regulatory RNA 1 Chr chromosome CI confidence interval CommCohort Community-Based Cohort COL6A2 collagen type VI alpha 2 chain FNDC3B fibronectin type III domain-containing protein 3B FOXC1 Forkhead Box C1 GAS7 growth arrest specific 7 GWAS genome-wide association study IOP intraocular pressure OMIM Online Mendelian Inheritance in Man POAG primary open-angle glaucoma SNP single nucleotide polymorphism SEPT8 septin-8 TMM Tohoku Medical Megabank ToMMo Tohoku Medical Megabank Organization TLCD5 TLC domain containing 5 WNT7B Wnt family member 7B

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Antibiotic Treatment Drives the Diversification of the Human Gut Resistome

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Genomics, Proteomics & bioinformatics 2019年第1期17卷 39-51页

作者： Jun Li Elizabeth A.Rettedal Eric van der Helm Mostafa Ellabaan Gianni Panagiotou Morten O.A.Sommer Department of Infectious Diseases and Public Health Colleague of Veterinary Medicine and Life Sciences City Univerity of Hong Kong School of Data Science City Univerity of Hong Kong Novo Nordisk Foundation Center for Biosustainability Systems Biology and Bioinformatics Unit Leibniz Institute for Natural Product Research and Infection Biology – Hans Kn?ll Institute Systems Biology and Bioinformatics Group School of Biological Sciences Faculty of Sciences The University of Hong Kong Department of Microbiology Li Ka Shing Faculty of Medicine The University of Hong Kong

Despite the documented antibiotic-induced disruption of the gut microbiota, the impact of antibiotic intake on strain-level dynamics, evolution of resistance genes, and factors influencing resistance dissemination potential remains poorly understood. To address this gap we analyzed public metagenomic datasets from 24 antibiotic treated subjects and controls, combined with an in-depth prospective functional study with two subjects investigating the bacterial community dynamics based on cultivation-dependent and independent methods. We observed that shortterm antibiotic treatment shifted and diversified the resistome composition, increased the average copy number of antibiotic resistance genes, and altered the dominant strain genotypes in an individual-specific manner. More than 30% of the resistance genes underwent strong differentiation at the single nucleotide level during antibiotic treatment. We found that the increased potential for horizontal gene transfer, due to antibiotic administration, was ～3-fold stronger in the differentiated resistance genes than the non-differentiated ones. This study highlights how antibiotic treatment has individualized impacts on the resistome and strain level composition, and drives the adaptive evolution of the gut microbiota.

关键词： Antibiotics Resistome Gut microbiome Strain Evolution Horizontal gene transfer

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Regression with a right-censored predictor, using inverse probability weighting methods

arXiv

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arXiv 2020年

作者： Matsouaka, Roland A. Atem, Folefac D. Department of Biostatistics and Bioinformatics & Program for Comparative Effectiveness Methodology Duke Clinical Research Institute Duke University DurhamNC United States Department of Biostatistics and Data Science University of Texas Health Science Center at Houston HoustonTX United States

In a longitudinal study, measures of key variables might be incomplete or partially recorded due to drop-out, loss to follow-up, or early termination of the study occurring before the advent of the event of interest. In this paper, we focus primarily on the implementation of a regression model with a randomly censored predictor. We examine, particularly, the use of inverse probability weighting methods in a generalized linear model (GLM), when the predictor of interest is right-censored, to adjust for censoring. To improve the performance of the complete-case analysis and prevent selection bias, we consider three different weighting schemes: inverse censoring probability weights, Kaplan-Meier weights, and Cox proportional hazards weights. We use Monte Carlo simulation studies to evaluate and compare the empirical properties of different weighting estimation methods. Finally, we apply these methods to the Framingham Heart Study data as an illustrative example to estimate the relationship between age of onset of a clinically diagnosed cardiovascular event and low-density lipoprotein (LDL) among cigarette smokers. Copyright © 2020, The Authors. All rights reserved.

关键词： Monte Carlo methods

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Local two-sample testing over graphs and point-clouds by random-walk distributions

arXiv

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arXiv 2020年

作者： Landa, Boris Qu, Rihao Chang, Joseph Kluger, Yuval Program in Applied Mathematics Yale University Department of Pathology Yale University School of Medicine Department of Statistics and Data Science Yale University Interdepartmental Program in Computational Biology and Bioinformatics Yale University Department of Immunology Yale School of Medicine

Rejecting the null hypothesis in two-sample testing is a fundamental tool for scientific discovery. Yet, aside from concluding that two samples do not come from the same probability distribution, it is often of interest to characterize how the two distributions differ. Given samples from two densities f1and f0, we consider the task of localizing occurrences of the inequality f1> f0. To avoid the challenges associated with high-dimensional space, we propose a general hypothesis testing framework where hypotheses are formulated adaptively to the data by conditioning on the combined sample from the two densities. We then investigate a special case of this framework where the notion of locality is captured by a random walk on a weighted graph constructed over this combined sample. We derive a tractable testing procedure for this case employing a type of scan statistic, and provide non-asymptotic lower bounds on the power and accuracy of our test to detect whether f1> f0in a local sense. Furthermore, we characterize the test's consistency according to a certain problem-hardness parameter, and show that our test achieves the minimax detection rate for this parameter. We conduct numerical experiments to validate our method, and demonstrate our approach on two real-world applications: detecting and localizing arsenic well contamination across the United States, and analyzing two-sample single-cell RNA sequencing data from melanoma *** Codes 62G10 Copyright © 2020, The Authors. All rights reserved.

关键词： Random processes

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Treatment outcomes of HIV patients with hepatitis B and C virus co-infections in Southwest China:an observational cohort study

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Infectious Diseases of Poverty 2022年第1期11卷 27-33页

作者： Jingya Jia Qiuying Zhu Luojia Deng Guanghua Lan Andrew Johnson Huanhuan Chen Zhiyong Shen Jianjun Li Hui Xing Yuhua Ruan Jing Li Hui Lu Sten H.Vermund Jinhui Zhu Han-Zhu Qian SJTU-Yale Joint Center for Biostatistics and Data Science Shanghai Jiao Tong UniversityShanghaiChina Department of Bioinformatics and Biostatistics School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghaiChina Guangxi Key Laboratory of Major Infectious Disease Prevention Control and Biosafety Emergency Response Guangxi Center for Disease Control and PreventionNanningChina Groton School GrotonMAUSA State Key Laboratory of Infectious Disease Prevention and Control(SKLID) Chinese Center for Disease Control and Prevention(China CDC)Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesBeijingChina School of Public Health Yale UniversityNew HavenCTUSA

Background:Antiretroviral therapy(ART)has reduced mortality among people living with HIV(PLWH)in China,but co-infections of hepatitis B virus(HBV)and hepatitis C virus(HCV)may individually or jointly reduce the effect of *** study aimed to evaluate the impacts of HBV/HCV coinfections on treatment drop-out and mortality among PLWH on ***:A retrospective cohort study analysis of 58,239 people living with HIV(PLWH)who initiated antiretroviral therapy(ART)during 2010-2018 was conducted in Guangxi Province,*** were from the observational database of the National Free Antiretroviral Treatment *** proportional hazard models were fitted to evaluate the effects of baseline infection of HBV or HCV or both on death and treatment attrition among ***:Our study showed high prevalence of HBV(11.5%),HCV(6.6%)and HBV-HCV(1.5%)*** overall mortality rate and treatment attrition rate was 2.95[95%confidence interval(CI):2.88-3.02]and 5.92(95%CI:5.82-6.01)per 100 person-years,*** with HIV-only patients,HBV-co-infected patients had 42%higher mortality[adjusted hazard ratio(a HR)=1.42;95%CI 1.32-1.54],HCV-co-infected patients had 65%higher mortality(a HR=1.65;95%CI:1.47-1.86),and patients with both HCV and HBV co-infections had 123%higher mortality(a HR=2.23;95%CI:1.87-2.66).Conclusions:HBV and HCV coinfection may have an additive effect on increasing the risk of all-cause death among PLWH who are on *** is suggested that there is need for primary prevention and access to effective hepatitis treatment for PLWH.

关键词： Hepatitis C virus Hepatitis B virus HIV Antiretroviral therapy Mortality Retrospective cohort

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Bovine Blastocyst Like Structures Derived From Stem Cell Cultures

SSRN

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SSRN 2023年

作者： Pinzón-Arteaga, Carlos A. Wang, Yinjuan Wei, Yulei Li, Leijie Orsi, Ana Elisa Ribeiro Scatolin, Giovanna Liu, Lizhong Sakurai, Masahiro Ye, Jianfeng Yu, Leqian Li, Bo Jiang, Zongliang Wu, Jun Department of Molecular Biology University of Texas Southwestern Medical Center DallasTX United States School of Animal Sciences AgCenter Louisiana State University Baton RougeLA70810 United States SJTU-Yale Joint Center for Biostatistics and Data Science School of Life Sciences and Biotechnology Shanghai Jiao Tong University Shanghai China Department of Genetics and Evolutionary Biology Institute of Biosciences University of São Paulo São Paulo Brazil Lyda Hill Department of Bioinformatics University of Texas Southwestern Medical Center DallasTX United States Department of Animal Sciences Genetics Institute University of Florida GainesvilleFL32610 United States Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical Center DallasTX75390 United States Cecil H. and Ida Green Center for Reproductive Biology Sciences University of Texas Southwestern Medical Center DallasTX United States

Understanding blastocyst formation and implantation is critical for improving farm animal reproduction but is hampered by a limited supply of embryos. We developed an efficient method to generate bovine blastocyst-like structures (termed blastoids) via the assembly of trophoblast stem cells and expanded potential stem cells. Bovine blastoids resemble blastocysts in morphology, cell composition, single-cell transcriptomes, and represent an accessible in vitro model for studying bovine embryogenesis © 2023, The Authors. All rights reserved.

关键词： Stem cells

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Relative Timing Information and Orthology in Evolutionary Scenarios

arXiv

引用

arXiv 2022年

作者： Schaller, David Hartmann, Tom Lafond, Manuel Wieseke, Nicolas Stadler, Peter F. Hellmuth, Marc Bioinformatics Group Department of Computer Science Interdisciplinary Center for Bioinformatics Universität Leipzig Härtelstraße 16–18 LeipzigD-04107 Germany Max Planck Institute for Mathematics in the Sciences Inselstraße 22 LeipzigD-04103 Germany Department of Computer Science Université de Sherbrooke 2500 boul. de l’Université SherbrookeQCJ1K 2R1 Canada Halle-Jena-Leipzig Competence Center for Scalable Data Services and Solutions Dresden-Leipzig Leipzig Research Center for Civilization Diseases Centre for Biotechnology and Biomedicine Leipzig University Universität Leipzig Germany Institute for Theoretical Chemistry University of Vienna Währingerstrasse 17 WienA-1090 Austria Facultad de Ciencias Universidad National de Colombia Sede Bogotá Colombia Santa Fe Insitute 1399 Hyde Park Rd. Santa FeNM87501 United States Swarm Intelligence and Complex Systems Group Department of Computer Science Leipzig University Augustusplatz 10 LeipzigD-04109 Germany Department of Mathematics Faculty of Science Stockholm University StockholmSE - 106 91 Sweden

Evolutionary scenarios describing the evolution of a family of genes within a collection of species comprise the mapping of the vertices of a gene tree T to vertices and edges of a species tree S. The relative timing of the last common ancestors of two extant genes (leaves of T) and the last common ancestors of the two species (leaves of S) in which they reside is indicative of horizontal gene transfers (HGT) and ancient duplications. Orthologous gene pairs, on the other hand, require that their last common ancestors coincides with a corresponding speciation event. The relative timing information of gene and species divergences is captured by three colored graphs that have the extant genes as vertices and the species in which the genes are found as vertex colors: the equal-divergence-time (EDT) graph, the later-divergence-time (LDT) graph and the prior-divergence-time (PDT) graph, which together form an edge partition of the complete graph. Here we give a complete characterization in terms of informative and forbidden triples that can be read off the three graphs and provide a polynomial time algorithm for constructing an evolutionary scenario that explains the graphs, provided such a scenario exists. While both LDT and PDT graphs are cographs, this is not true for the EDT graph in general. We show that every EDT graph is perfect. While the information about LDT and PDT graphs is necessary to recognize EDT graphs in polynomial-time for general scenarios, this extra information can be dropped in the HGT-free case. However, recognition of EDT graphs without knowledge of putative LDT and PDT graphs is NP-complete for general scenarios. In contrast, PDT graphs can be recognized in polynomial-time. We finally connect the EDT graph to the alternative definitions of orthology that have been proposed for scenarios with horizontal gene transfer. With one exception, the corresponding graphs are shown to be colored cographs. © 2022, CC BY.

关键词： Genes

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Implementation of online learning during the COVID-19 pandemic in primary schools

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AIP Conference Proceedings 2023年第1期2594卷

作者： A. Anugrahana E. Liswantiani D. Sudigyo T. Suparyanto B. Pardamean Elementary School Teacher Education Study Program (PGSD) Faculty of Teacher Training and Education Sanata Dharma University Yogyakarta Indonesia 55281 Bioinformatics & Data Science Research Center Bina Nusantara University Jakarta Indonesia 11480 Computer Science Department BINUS Graduate Program - Master of Computer Science Program Bina Nusantara University Jakarta Indonesia 11480

The COVID-19 pandemic requires face-to-face learning to shift to online or distance learning. Therefore, the elementary school, which is the most basic level of education affected by this phenomenon, where this research is carried out. This study aimed to analyze the process of implementing online learning, the supporting and inhibiting factors for teachers, students, and parents in implementing online learning during the COVID-19 pandemic. In addition, good practices for online learning were also analyzed in this study to understand these phenomena in elementary schools. The research method utilized descriptive qualitative research and was performed at a private primary school in Yogyakarta. The subjects consisted of teachers, students, and parents that were involved in the online learning process. Online questionnaires and interviews were used to collect data. The results of this study show the enormous impact of the COVID-19 pandemic on the learning process. Learning that is usually carried out face-to-face (conventional) has now been converted into online learning in elementary school.

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Shapley variable importance clouds for interpretable machine learning

arXiv

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arXiv 2021年

作者： Ning, Yilin Ong, Marcus Eng Hock Chakraborty, Bibhas Goldstein, Benjamin Alan Ting, Daniel Shu Wei Vaughan, Roger Liu, Nan Centre for Quantitative Medicine Duke-NUS Medical School Singapore Singapore Programme in Health Services and Systems Research Duke-NUS Medical School Singapore Singapore Health Services Research Centre Singapore Health Services Singapore Singapore Department of Emergency Medicine Singapore General Hospital Singapore Singapore Department of Statistics and Data Science National University of Singapore Singapore Singapore Department of Biostatistics and Bioinformatics Duke University DurhamNC United States SingHealth Ai Health Program Singapore Health Services Singapore Singapore Institute of Data Science National University of Singapore Singapore Singapore

Interpretable machine learning has been focusing on explaining final models that optimize performance. The current state-of-the-art is the Shapley additive explanations (SHAP) that locally explains variable impact on individual predictions, and it is recently extended for a global assessment across the dataset. Recently, Dong and Rudin proposed to extend the investigation to models from the same class as the final model that are "good enough", and identified a previous overclaim of variable importance based on a single model. However, this method does not directly integrate with existing Shapley-based interpretations. We close this gap by proposing a Shapley variable importance cloud that pools information across good models to avoid biased assessments in SHAP analyses of final models, and communicate the findings via novel visualizations. We demonstrate the additional insights gain compared to conventional explanations and Dong and Rudin's method using criminal justice and electronic medical records data. © 2021, CC BY.

关键词： Medical computing

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