A major issue in the use of immune checkpoint inhibitors is their lack of efficacy in many patients. Previous studies have reported that the T cell inflamed signature can help predict the response to immunotherapy. Thus, many studies have investigated mechanisms of immunotherapy resistance by defining the tumor microenvironment based on T cell inflamed and non–T cell inflamed subsets. Although methods of calculating T cell inflamed subsets have been developed, valid screening tools for distinguishing T cell inflamed from non–T cell inflamed subsets using gene expression data are still needed, since general researchers who are unfamiliar with the details of the equations can experience difficulties using extant scoring formulas to conduct analyses. Thus, we introduce TcellInflamedDetector, an R package for distinguishing T cell inflamed from non–T cell inflamed samples using cancer gene expression data via bulk RNA sequencing.
{"title":"TcellInflamedDetector: an R package to distinguish T cell inflamed tumor types from non–T cell inflamed tumor types","authors":"San-Duk Yang, Hyun-Seok Park","doi":"10.5808/gi.22005","DOIUrl":"https://doi.org/10.5808/gi.22005","url":null,"abstract":"A major issue in the use of immune checkpoint inhibitors is their lack of efficacy in many patients. Previous studies have reported that the T cell inflamed signature can help predict the response to immunotherapy. Thus, many studies have investigated mechanisms of immunotherapy resistance by defining the tumor microenvironment based on T cell inflamed and non–T cell inflamed subsets. Although methods of calculating T cell inflamed subsets have been developed, valid screening tools for distinguishing T cell inflamed from non–T cell inflamed subsets using gene expression data are still needed, since general researchers who are unfamiliar with the details of the equations can experience difficulties using extant scoring formulas to conduct analyses. Thus, we introduce TcellInflamedDetector, an R package for distinguishing T cell inflamed from non–T cell inflamed samples using cancer gene expression data via bulk RNA sequencing.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45472943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-18DOI: 10.21203/rs.3.rs-602073/v1
M. Kader, Akash Ahammed, Md. Sharif Khan, Sheikh Abdullah Al Ashik, M. Islam, Mohammad Uzzal Hossain
Litorilituus sediminis is a Gram-negative, aerobic, novel bacterium under the family of Colwelliaceae, has a stunning hypothetical protein containing domain called von Hippel-Lindau that has significant tumor suppressor activity. Therefore, this study was designed to elucidate the structure and function of the biologically important hypothetical protein EMK97_00595 (QBG34344.1) using several bioinformatics tools. The functional annotation exposed that the hypothetical protein is an extracellular secretory soluble signal peptide and contains the von Hippel-Lindau (VHL; VHL beta) domain that has a significant role in tumor suppression. This domain is conserved throughout evolution, as its homologs are available in various types of the organism like mammals, insects, and nematode. The gene product of VHL has a critical regulatory activity in the ubiquitous oxygen-sensing pathway. This domain has a significant role in inhibiting cell proliferation, angiogenesis progression, kidney cancer, breast cancer, and colon cancer. At last, the current study depicts that the annotated hypothetical protein is linked with tumor suppressor activity which might be of great interest to future research in the higher organism.
{"title":"Hypothetical protein predicted to be tumor suppressor: a protein functional analysis","authors":"M. Kader, Akash Ahammed, Md. Sharif Khan, Sheikh Abdullah Al Ashik, M. Islam, Mohammad Uzzal Hossain","doi":"10.21203/rs.3.rs-602073/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-602073/v1","url":null,"abstract":"Litorilituus sediminis is a Gram-negative, aerobic, novel bacterium under the family of Colwelliaceae, has a stunning hypothetical protein containing domain called von Hippel-Lindau that has significant tumor suppressor activity. Therefore, this study was designed to elucidate the structure and function of the biologically important hypothetical protein EMK97_00595 (QBG34344.1) using several bioinformatics tools. The functional annotation exposed that the hypothetical protein is an extracellular secretory soluble signal peptide and contains the von Hippel-Lindau (VHL; VHL beta) domain that has a significant role in tumor suppression. This domain is conserved throughout evolution, as its homologs are available in various types of the organism like mammals, insects, and nematode. The gene product of VHL has a critical regulatory activity in the ubiquitous oxygen-sensing pathway. This domain has a significant role in inhibiting cell proliferation, angiogenesis progression, kidney cancer, breast cancer, and colon cancer. At last, the current study depicts that the annotated hypothetical protein is linked with tumor suppressor activity which might be of great interest to future research in the higher organism.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48638779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-06DOI: 10.1101/2020.01.06.895698
H. Jeong, Jinseon Yoo, Hyunwoo J. Kim, Tae-Min Kim
Mutation signatures represent unique sequence footprints of somatic mutations resulting from specific DNA mutagenic and repair processes; however, their causal associations and potential utility for genome research remain largely unknown. In this study, we performed PanCancer-scale correlative analyses to identify the genomic features associated with tumor mutation burdens (TMB) and individual mutation signatures. We observed that TMB was correlated with tumor purity, ploidy, and the level of aneuploidy, as well as with the expression of cell proliferation-related genes representing genomic covariates in evaluating TMB. Correlative analyses of mutation signature levels with genes belonging to DNA damage-repair processes revealed that deficiencies of NHEJ1 and ALKBH3 may elevate TMB levels in cancer genomes accompanying APOBEC overactivity and DNA mismatch repair deficiency, respectively. We further employed a strategy to identify feature-driven, de novo mutation signatures and demonstrated they can be reconstructed using known causal features such as APOBEC overexpression, MLH1 underexpression, POLE mutations, and the level of homologous recombination deficiency. We further demonstrated, that tumor hypoxia-related mutation signatures are similar to those associated with APOBEC suggesting that APOBEC-related mutagenic activity mediates hypoxia-related mutational consequences in cancer genomes, and also, that mutation signatures can be further used to predict hypoxic tumors. Taken together, our study advances mutation signature-level mechanistic insights in cancer genomes, extending categories of cancer-relevant mutation signatures and their potential biological implications. Author summary Mutation signature analysis is powerful in deciphering the causative mutagenic events and their contributions in individual cancer genomes, but the causal relationship of individual mutation signatures are still largely unknown. PanCancer-scaled correlative analysis revealed mutation resource candidates in cancer genomes such as NHEJ1 and ALKBH3 deficiencies that may facilitate the accumulation of mutations in the setting of APOBEC overactivity and DNA mismatch repair deficiency, respectively. A feature-driven mutation discovery approach was employed to identify the mutation signatures representing homologous recombination deficiency and tumor hypoxia, the extent of which may serve as mutation-based phenotypic measures, previously estimated by DNA copy number alterations and mRNA expression signatures, respectively. Our study advances our understanding into the mechanistic insights of mutation signatures and proposes a method to utilize somatic mutations as a molecular proxy in terms of mutation signatures.
{"title":"Correlation-based and feature-driven mutation signature analyses to identify genetic features associated with DNA mutagenic processes in cancer genomes","authors":"H. Jeong, Jinseon Yoo, Hyunwoo J. Kim, Tae-Min Kim","doi":"10.1101/2020.01.06.895698","DOIUrl":"https://doi.org/10.1101/2020.01.06.895698","url":null,"abstract":"Mutation signatures represent unique sequence footprints of somatic mutations resulting from specific DNA mutagenic and repair processes; however, their causal associations and potential utility for genome research remain largely unknown. In this study, we performed PanCancer-scale correlative analyses to identify the genomic features associated with tumor mutation burdens (TMB) and individual mutation signatures. We observed that TMB was correlated with tumor purity, ploidy, and the level of aneuploidy, as well as with the expression of cell proliferation-related genes representing genomic covariates in evaluating TMB. Correlative analyses of mutation signature levels with genes belonging to DNA damage-repair processes revealed that deficiencies of NHEJ1 and ALKBH3 may elevate TMB levels in cancer genomes accompanying APOBEC overactivity and DNA mismatch repair deficiency, respectively. We further employed a strategy to identify feature-driven, de novo mutation signatures and demonstrated they can be reconstructed using known causal features such as APOBEC overexpression, MLH1 underexpression, POLE mutations, and the level of homologous recombination deficiency. We further demonstrated, that tumor hypoxia-related mutation signatures are similar to those associated with APOBEC suggesting that APOBEC-related mutagenic activity mediates hypoxia-related mutational consequences in cancer genomes, and also, that mutation signatures can be further used to predict hypoxic tumors. Taken together, our study advances mutation signature-level mechanistic insights in cancer genomes, extending categories of cancer-relevant mutation signatures and their potential biological implications. Author summary Mutation signature analysis is powerful in deciphering the causative mutagenic events and their contributions in individual cancer genomes, but the causal relationship of individual mutation signatures are still largely unknown. PanCancer-scaled correlative analysis revealed mutation resource candidates in cancer genomes such as NHEJ1 and ALKBH3 deficiencies that may facilitate the accumulation of mutations in the setting of APOBEC overactivity and DNA mismatch repair deficiency, respectively. A feature-driven mutation discovery approach was employed to identify the mutation signatures representing homologous recombination deficiency and tumor hypoxia, the extent of which may serve as mutation-based phenotypic measures, previously estimated by DNA copy number alterations and mRNA expression signatures, respectively. Our study advances our understanding into the mechanistic insights of mutation signatures and proposes a method to utilize somatic mutations as a molecular proxy in terms of mutation signatures.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48497540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-01DOI: 10.5808/GI.2019.17.3.e24
Ho-Sun Lee
Early environmental exposure is recognized as a key factor for long-term health based on the Developmental Origins of Health and Disease hypothesis. It considers that early-life nutrition is now being recognized as a major contributor that may permanently program change of organ structure and function toward the development of diseases, in which epigenetic mechanisms are involved. Recent researches indicate early-life environmental factors modulate the microbiome development and the microbiome might be mediate diet-epigenetic interaction. This review aims to define which nutrients involve microbiome development during the critical window of susceptibility to disease, and how microbiome modulation regulates epigenetic changes and influences human health and future prevention strategies.
{"title":"The interaction between gut microbiome and nutrients on development of human disease through epigenetic mechanisms","authors":"Ho-Sun Lee","doi":"10.5808/GI.2019.17.3.e24","DOIUrl":"https://doi.org/10.5808/GI.2019.17.3.e24","url":null,"abstract":"Early environmental exposure is recognized as a key factor for long-term health based on the Developmental Origins of Health and Disease hypothesis. It considers that early-life nutrition is now being recognized as a major contributor that may permanently program change of organ structure and function toward the development of diseases, in which epigenetic mechanisms are involved. Recent researches indicate early-life environmental factors modulate the microbiome development and the microbiome might be mediate diet-epigenetic interaction. This review aims to define which nutrients involve microbiome development during the critical window of susceptibility to disease, and how microbiome modulation regulates epigenetic changes and influences human health and future prevention strategies.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42891114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-01DOI: 10.5808/gi.2019.17.3.e27
Doori Park, Jong-Hwa Kim, Nam-Soo Kim
Supernumerary B chromosomes were found in Lilium amabile (2n = 2x = 24), an endemic Korean lily that grows in the wild throughout the Korean Peninsula. The extra B chromosomes do not affect the host-plant morphology; therefore, whole transcriptome analysis was performed in 0B and 1B plants to identify differentially expressed genes. A total of 154,810 transcripts were obtained from over 10 Gbp data by de novo assembly. By mapping the raw reads to the de novo transcripts, we identified 7,852 differentially expressed genes (log2FC > |10|), in which 4,059 and 3,794 were up-and down-regulated, respectively, in 1B plants compared to 0B plants. Functional enrichment analysis revealed that various differentially expressed genes were involved in cellular processes including the cell cycle, chromosome breakage and repair, and microtubule formation; all of which may be related to the occurrence and maintenance of B chromosomes. Our data provide insight into transcriptomic changes and evolution of plant B chromosomes and deliver an informative database for future study of B chromosome transcriptomes in the Korean lily.
{"title":"De novo transcriptome sequencing and gene expression profiling with/without B-chromosome plants of Lilium amabile","authors":"Doori Park, Jong-Hwa Kim, Nam-Soo Kim","doi":"10.5808/gi.2019.17.3.e27","DOIUrl":"https://doi.org/10.5808/gi.2019.17.3.e27","url":null,"abstract":"Supernumerary B chromosomes were found in Lilium amabile (2n = 2x = 24), an endemic Korean lily that grows in the wild throughout the Korean Peninsula. The extra B chromosomes do not affect the host-plant morphology; therefore, whole transcriptome analysis was performed in 0B and 1B plants to identify differentially expressed genes. A total of 154,810 transcripts were obtained from over 10 Gbp data by de novo assembly. By mapping the raw reads to the de novo transcripts, we identified 7,852 differentially expressed genes (log2FC > |10|), in which 4,059 and 3,794 were up-and down-regulated, respectively, in 1B plants compared to 0B plants. Functional enrichment analysis revealed that various differentially expressed genes were involved in cellular processes including the cell cycle, chromosome breakage and repair, and microtubule formation; all of which may be related to the occurrence and maintenance of B chromosomes. Our data provide insight into transcriptomic changes and evolution of plant B chromosomes and deliver an informative database for future study of B chromosome transcriptomes in the Korean lily.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45989871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-01DOI: 10.5808/gi.2019.17.3.e29
Chloe Soohyun Jang, Wanson Choi, Seungho Cook, B. Han
The Wellcome Trust Case Control Consortium (WTCCC) study was a large genome-wide association study that aimed to identify common variants associated with seven diseases. That study combined two control datasets (58C and UK Blood Services) as shared controls. Prior to using the combined controls, the WTCCC performed analyses to show that the genomic content of the control datasets was not significantly different. Recently, the analysis of human leukocyte antigen (HLA) genes has become prevalent due to the development of HLA imputation technology. In this project, we extended the between-control homogeneity analysis of the WTCCC to HLA. We imputed HLA information in the WTCCC control dataset and showed that the HLA content was not significantly different between the two control datasets, suggesting that the combined controls can be used as controls for HLA fine-mapping analysis based on HLA imputation.
{"title":"Analysis of differences in human leukocyte antigen between the two Wellcome Trust Case Control Consortium control datasets","authors":"Chloe Soohyun Jang, Wanson Choi, Seungho Cook, B. Han","doi":"10.5808/gi.2019.17.3.e29","DOIUrl":"https://doi.org/10.5808/gi.2019.17.3.e29","url":null,"abstract":"The Wellcome Trust Case Control Consortium (WTCCC) study was a large genome-wide association study that aimed to identify common variants associated with seven diseases. That study combined two control datasets (58C and UK Blood Services) as shared controls. Prior to using the combined controls, the WTCCC performed analyses to show that the genomic content of the control datasets was not significantly different. Recently, the analysis of human leukocyte antigen (HLA) genes has become prevalent due to the development of HLA imputation technology. In this project, we extended the between-control homogeneity analysis of the WTCCC to HLA. We imputed HLA information in the WTCCC control dataset and showed that the HLA content was not significantly different between the two control datasets, suggesting that the combined controls can be used as controls for HLA fine-mapping analysis based on HLA imputation.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43993747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We sought the novel concept, transcript capacity (TC) and analyzed TC. Our approach to estimate TC was through an in silico method. TC refers to the capacity that a transcript exerts in a cell as enzyme or protein function after translation. We used the genome-wide association study (GWAS) beta effect and transcription level in RNA-sequencing to estimate TC. The trait was body fat percent and the transcript reads were obtained from the human protein atlas. The assumption was that the GWAS beta effect is the gene’s effect and TC was related to the corresponding gene effect and transcript reads. Further, we surveyed gene ontology (GO) in the highest TC and the lowest TC genes. The most frequent GOs with the highest TC were neuronal-related and cell projection organization related. The most frequent GOs with the lowest TC were wound-healing related and embryo development related. We expect that our analysis contributes to estimating TC in the diverse species and playing a benevolent role to the new bioinformatic analysis.
{"title":"In silico approach to calculate the transcript capacity","authors":"Young-Sup Lee, Kyung-Hye Won, Jae-Don Oh, Donghyun Shin","doi":"10.5808/GI.2019.17.3.e31","DOIUrl":"https://doi.org/10.5808/GI.2019.17.3.e31","url":null,"abstract":"We sought the novel concept, transcript capacity (TC) and analyzed TC. Our approach to estimate TC was through an in silico method. TC refers to the capacity that a transcript exerts in a cell as enzyme or protein function after translation. We used the genome-wide association study (GWAS) beta effect and transcription level in RNA-sequencing to estimate TC. The trait was body fat percent and the transcript reads were obtained from the human protein atlas. The assumption was that the GWAS beta effect is the gene’s effect and TC was related to the corresponding gene effect and transcript reads. Further, we surveyed gene ontology (GO) in the highest TC and the lowest TC genes. The most frequent GOs with the highest TC were neuronal-related and cell projection organization related. The most frequent GOs with the lowest TC were wound-healing related and embryo development related. We expect that our analysis contributes to estimating TC in the diverse species and playing a benevolent role to the new bioinformatic analysis.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49468368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-01Epub Date: 2019-09-27DOI: 10.5808/GI.2019.17.3.e32
Sol A Jeon, Jong Lyul Park, Jong-Hwan Kim, Jeong Hwan Kim, Yong Sung Kim, Jin Cheon Kim, Seon-Young Kim
Currently, Illumina sequencers are the globally leading sequencing platform in the next-generation sequencing market. Recently, MGI Tech launched a series of new sequencers, including the MGISEQ-2000, which promise to deliver high-quality sequencing data faster and at lower prices than Illumina's sequencers. In this study, we compared the performance of two major sequencers (MGISEQ-2000 and HiSeq 4000) to test whether the MGISEQ-2000 sequencer delivers high-quality sequence data as suggested. We performed RNA sequencing of four human colon cancer samples with the two platforms, and compared the sequencing quality and expression values. The data produced from the MGISEQ-2000 and HiSeq 4000 showed high concordance, with Pearson correlation coefficients ranging from 0.98 to 0.99. Various quality control (QC) analyses showed that the MGISEQ-2000 data fulfilled the required QC measures. Our study suggests that the performance of the MGISEQ-2000 is comparable to that of the HiSeq 4000 and that the MGISEQ-2000 can be a useful platform for sequencing.
{"title":"Comparison of the MGISEQ-2000 and Illumina HiSeq 4000 sequencing platforms for RNA sequencing.","authors":"Sol A Jeon, Jong Lyul Park, Jong-Hwan Kim, Jeong Hwan Kim, Yong Sung Kim, Jin Cheon Kim, Seon-Young Kim","doi":"10.5808/GI.2019.17.3.e32","DOIUrl":"https://doi.org/10.5808/GI.2019.17.3.e32","url":null,"abstract":"<p><p>Currently, Illumina sequencers are the globally leading sequencing platform in the next-generation sequencing market. Recently, MGI Tech launched a series of new sequencers, including the MGISEQ-2000, which promise to deliver high-quality sequencing data faster and at lower prices than Illumina's sequencers. In this study, we compared the performance of two major sequencers (MGISEQ-2000 and HiSeq 4000) to test whether the MGISEQ-2000 sequencer delivers high-quality sequence data as suggested. We performed RNA sequencing of four human colon cancer samples with the two platforms, and compared the sequencing quality and expression values. The data produced from the MGISEQ-2000 and HiSeq 4000 showed high concordance, with Pearson correlation coefficients ranging from 0.98 to 0.99. Various quality control (QC) analyses showed that the MGISEQ-2000 data fulfilled the required QC measures. Our study suggests that the performance of the MGISEQ-2000 is comparable to that of the HiSeq 4000 and that the MGISEQ-2000 can be a useful platform for sequencing.</p>","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"17 3","pages":"e32"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41224609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：