Fuzzy C-Means(FCM)is an effective and widely used clustering algorithm,but there are still some problems.considering the number of clusters must be determined manually,the local optimal solutions is easily influenced ...Fuzzy C-Means(FCM)is an effective and widely used clustering algorithm,but there are still some problems.considering the number of clusters must be determined manually,the local optimal solutions is easily influenced by the random selection of initial cluster centers,and the performance of Euclid distance in complex high-dimensional data is poor.To solve the above problems,the improved FCM clustering algorithm based on density Canopy and Manifold learning(DM-FCM)is proposed.First,a density Canopy algorithm based on improved local density is proposed to automatically deter-mine the number of clusters and initial cluster centers,which improves the self-adaptability and stability of the algorithm.Then,considering that high-dimensional data often present a nonlinear structure,the manifold learning method is applied to construct a manifold spatial structure,which preserves the global geometric properties of complex high-dimensional data and improves the clustering effect of the algorithm on complex high-dimensional datasets.Fowlkes-Mallows Index(FMI),the weighted average of homogeneity and completeness(V-measure),Adjusted Mutual Information(AMI),and Adjusted Rand Index(ARI)are used as performance measures of clustering algorithms.The experimental results show that the manifold learning method is the superior distance measure,and the algorithm improves the clustering accuracy and performs superiorly in the clustering of low-dimensional and complex high-dimensional data.展开更多
Solid organ transplant(SOT)recipients receive immunosuppressive drugs(ISDs)and are susceptible to developing severe COVID-19.Here,we analyze the Spike-specific T-cell response after 3 doses of mRNA vaccine in a group ...Solid organ transplant(SOT)recipients receive immunosuppressive drugs(ISDs)and are susceptible to developing severe COVID-19.Here,we analyze the Spike-specific T-cell response after 3 doses of mRNA vaccine in a group of SOT patients(n=136)treated with different ISDs.We demonstrate that a combination of a calcineurin inhibitor(CNI),mycophenolate mofetil(MMF),and prednisone(Pred)treatment regimen strongly suppressed the mRNA vaccine-induced Spike-specific cellular response.Such defects have clinical consequences because the magnitude of vaccine-induced Spike-specific T cells was directly proportional to the ability of SOT patients to rapidly clear SARS-CoV-2 after breakthrough infection.To then compensate for the T-cell defects induced by immunosuppressive treatment and to develop an alternative therapeutic strategy for SOT patients,we describe production of 6 distinct SARS-CoV-2 epitope-specific ISD-resistant T-cell receptor(TCR)-T cells engineered using the mRNA electroporation method with reactivity minimally affected by mutations occurring in Beta,Delta,Gamma,and Omicron variants.This strategy with transient expression characteristics marks an improvement in the immunotherapeutic field and provides an attractive and novel therapeutic possibility for immunosuppressed COVID-19 patients.展开更多
基金The National Natural Science Foundation of China(No.62262011)the Natural Science Foundation of Guangxi(No.2021JJA170130).
文摘Fuzzy C-Means(FCM)is an effective and widely used clustering algorithm,but there are still some problems.considering the number of clusters must be determined manually,the local optimal solutions is easily influenced by the random selection of initial cluster centers,and the performance of Euclid distance in complex high-dimensional data is poor.To solve the above problems,the improved FCM clustering algorithm based on density Canopy and Manifold learning(DM-FCM)is proposed.First,a density Canopy algorithm based on improved local density is proposed to automatically deter-mine the number of clusters and initial cluster centers,which improves the self-adaptability and stability of the algorithm.Then,considering that high-dimensional data often present a nonlinear structure,the manifold learning method is applied to construct a manifold spatial structure,which preserves the global geometric properties of complex high-dimensional data and improves the clustering effect of the algorithm on complex high-dimensional datasets.Fowlkes-Mallows Index(FMI),the weighted average of homogeneity and completeness(V-measure),Adjusted Mutual Information(AMI),and Adjusted Rand Index(ARI)are used as performance measures of clustering algorithms.The experimental results show that the manifold learning method is the superior distance measure,and the algorithm improves the clustering accuracy and performs superiorly in the clustering of low-dimensional and complex high-dimensional data.
基金We would like to acknowledge the contribution of the Singapore National University Centre for Organ Transplantation team members who helped recruit patients:AV,AL,and WKK.We thank all voluntary blood donors for their donations.We would like to thank the members of AB’s lab for their insights and critique.Finally,we would also like to thank Dr.Yongxu Lu and Prof.Geoffrey L.Smith from the Department of Pathology,University of Cambridge,U.K.,for supplying the vaccinia virus-expressing Spike and Nucleocapsid proteins.This study was supported by research funding from the Singapore Ministry of Health’s National Medical Research Council MOH-000019(MOH-StaR17Nov-001)to Antonio BertolettiPart of this work was also supported by the A*ccelerate GAP-funded project(ACCL/19-GAP064-R20H-H)from the Agency of Science+1 种基金Technology and Research(A*STAR),the Singapore National Medical Research Council COVID-19 Research Fund(COVID19RF-011)a Start-up University Grant from the Ministry of Education(Singapore)to Laurent Renia.YSG was supported by a Career Development Fund award by A*STAR(SC35/22-805100).
文摘Solid organ transplant(SOT)recipients receive immunosuppressive drugs(ISDs)and are susceptible to developing severe COVID-19.Here,we analyze the Spike-specific T-cell response after 3 doses of mRNA vaccine in a group of SOT patients(n=136)treated with different ISDs.We demonstrate that a combination of a calcineurin inhibitor(CNI),mycophenolate mofetil(MMF),and prednisone(Pred)treatment regimen strongly suppressed the mRNA vaccine-induced Spike-specific cellular response.Such defects have clinical consequences because the magnitude of vaccine-induced Spike-specific T cells was directly proportional to the ability of SOT patients to rapidly clear SARS-CoV-2 after breakthrough infection.To then compensate for the T-cell defects induced by immunosuppressive treatment and to develop an alternative therapeutic strategy for SOT patients,we describe production of 6 distinct SARS-CoV-2 epitope-specific ISD-resistant T-cell receptor(TCR)-T cells engineered using the mRNA electroporation method with reactivity minimally affected by mutations occurring in Beta,Delta,Gamma,and Omicron variants.This strategy with transient expression characteristics marks an improvement in the immunotherapeutic field and provides an attractive and novel therapeutic possibility for immunosuppressed COVID-19 patients.
