Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci
- Breeze, Charles, Batorsky, Anna, Lee, Mi, Szeto, Mindy, Charchar, Fadi
- Authors: Breeze, Charles , Batorsky, Anna , Lee, Mi , Szeto, Mindy , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Genome Medicine Vol. 13, no. 1 (Apr 30 2021), p.
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- Description: Background DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. Methods The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. Results We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. Conclusions We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context.
Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci
- Authors: Breeze, Charles , Batorsky, Anna , Lee, Mi , Szeto, Mindy , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Genome Medicine Vol. 13, no. 1 (Apr 30 2021), p.
- Full Text:
- Reviewed:
- Description: Background DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. Methods The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. Results We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. Conclusions We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context.
Genomic diversity and antimicrobial resistance among non-typhoidal Salmonella associated with human disease in The Gambia
- Darboe, Saffiatou, Bradbury, Richard, Phelan, Jody, Kanteh, Abdoulie, Muhammad, Abdul-Khalie, Worwui, Archibald, Yang, Shangxin, Nwakanma, Davis, Perez-Sepulveda, Blanca, Kariuki, Samuel, Kwambana-Adams, Brenda, Antonio, Martin
- Authors: Darboe, Saffiatou , Bradbury, Richard , Phelan, Jody , Kanteh, Abdoulie , Muhammad, Abdul-Khalie , Worwui, Archibald , Yang, Shangxin , Nwakanma, Davis , Perez-Sepulveda, Blanca , Kariuki, Samuel , Kwambana-Adams, Brenda , Antonio, Martin
- Date: 2022
- Type: Text , Journal article
- Relation: Microbial Genomics Vol. 8, no. 3 (2022), p.
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- Description: Non-typhoidal Salmonella associated with multidrug resistance cause invasive disease in sub-Saharan Africa. Specific lineages of serovars Typhimurium and Enteritidis have been implicated. Here we characterized the genomic diversity of 100 clinical non-typhoidal Salmonella collected from 93 patients in 2001 from the eastern, and in 2006–2018 from the western regions of The Gambia respectively. A total of 93 isolates (64 invasive, 23 gastroenteritis and six other sites) representing a single infection episode were phenotypically tested for antimicrobial susceptibility using the Kirby–Bauer disc diffusion technique. Whole genome sequencing of 100 isolates was performed using Illumina, and the reads were assembled and analysed using SPAdes. The Salmonella in Silico Typing Resource (SISTR) was used for serotyping. SNP differences among the 93 isolates were determined using Roary, and phylogenetic analysis was performed in the context of 495 African strains from the European Nucleotide Archive. Salmonella serovars Typhimurium (26/64; 30.6%) and Enteritidis (13/64; 20.3%) were associated with invasive disease, whilst other serovars were mainly responsible for gastroenteritis (17/23; 73.9%). The presence of three major serovar Enteritidis clades was confirmed, including the invasive West African clade, which made up more than half (11/16; 68.8%) of the genomes. Multidrug resistance was confined among the serovar Enteritidis West African clade. The presence of this epidemic virulent clade has potential for spread of resistance and thus important implications for systematic patient management. Surveillance and epidemiological investigations to inform control are warranted. © 2022 The Authors.
- Authors: Darboe, Saffiatou , Bradbury, Richard , Phelan, Jody , Kanteh, Abdoulie , Muhammad, Abdul-Khalie , Worwui, Archibald , Yang, Shangxin , Nwakanma, Davis , Perez-Sepulveda, Blanca , Kariuki, Samuel , Kwambana-Adams, Brenda , Antonio, Martin
- Date: 2022
- Type: Text , Journal article
- Relation: Microbial Genomics Vol. 8, no. 3 (2022), p.
- Full Text:
- Reviewed:
- Description: Non-typhoidal Salmonella associated with multidrug resistance cause invasive disease in sub-Saharan Africa. Specific lineages of serovars Typhimurium and Enteritidis have been implicated. Here we characterized the genomic diversity of 100 clinical non-typhoidal Salmonella collected from 93 patients in 2001 from the eastern, and in 2006–2018 from the western regions of The Gambia respectively. A total of 93 isolates (64 invasive, 23 gastroenteritis and six other sites) representing a single infection episode were phenotypically tested for antimicrobial susceptibility using the Kirby–Bauer disc diffusion technique. Whole genome sequencing of 100 isolates was performed using Illumina, and the reads were assembled and analysed using SPAdes. The Salmonella in Silico Typing Resource (SISTR) was used for serotyping. SNP differences among the 93 isolates were determined using Roary, and phylogenetic analysis was performed in the context of 495 African strains from the European Nucleotide Archive. Salmonella serovars Typhimurium (26/64; 30.6%) and Enteritidis (13/64; 20.3%) were associated with invasive disease, whilst other serovars were mainly responsible for gastroenteritis (17/23; 73.9%). The presence of three major serovar Enteritidis clades was confirmed, including the invasive West African clade, which made up more than half (11/16; 68.8%) of the genomes. Multidrug resistance was confined among the serovar Enteritidis West African clade. The presence of this epidemic virulent clade has potential for spread of resistance and thus important implications for systematic patient management. Surveillance and epidemiological investigations to inform control are warranted. © 2022 The Authors.
Distinct Streptococcus pneumoniae cause invasive disease in Papua New Guinea
- Mellor, Kate, Lo, Stephanie, Yoannes, Mition, Michael, Audrey, Orami, Tilda, Greenhill, Andrew, Breiman, Robert, Hawkins, Paulina, McGee, Lesley, Bentley, Stephen, Ford, Rebecca, Lehmann, Deborah
- Authors: Mellor, Kate , Lo, Stephanie , Yoannes, Mition , Michael, Audrey , Orami, Tilda , Greenhill, Andrew , Breiman, Robert , Hawkins, Paulina , McGee, Lesley , Bentley, Stephen , Ford, Rebecca , Lehmann, Deborah
- Date: 2022
- Type: Text , Journal article
- Relation: Microbial Genomics Vol. 8, no. 7 (2022), p.
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- Description: Streptococcus pneumoniae is a key contributor to childhood morbidity and mortality in Papua New Guinea (PNG). For the first time, whole genome sequencing of 174 isolates has enabled detailed characterisation of diverse S. pneumoniae causing invasive disease in young children in PNG, 1989-2014. This study captures the baseline S. pneumoniae population prior to the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the national childhood immunisation programme in 2014. Relationships amongst lineages, serotypes and antimicrobial resistance traits were characterised, and the population was viewed in the context of a global collection of isolates. The analyses highlighted adiverse S. pneumoniae population associated with invasive disease in PNG, with 45 unique Global Pneumococcal Sequence Clusters (GPSCs) observed amongst the 174 isolates reflecting multiple lineages observed in PNG that have not been identified in other geographic locations. The majority of isolates were from children with meningitis, of which 52% (n=72) expressed non-PCV13 serotypes. Over a third of isolates were predicted to be resistant to at least one antimicrobial. PCV13 serotype isolates had 10.1 times the odds of being multidrug-resistant (MDR) compared to non-vaccine serotype isolates, and no isolates with GPSCs unique to PNG were MDR. Serotype 2 was the most commonly identified serotype; we identified a highly clonal cluster of serotype 2 isolates unique to PNG, and a distinct second cluster indicative of long-distance transmission. Ongoing surveillance, including whole-genome sequencing, is needed to ascertain the impact of the national PCV13 programme upon the S. pneumoniae population, including serotype replacement and antimicrobial resistance traits. © 2022 The Authors.
- Authors: Mellor, Kate , Lo, Stephanie , Yoannes, Mition , Michael, Audrey , Orami, Tilda , Greenhill, Andrew , Breiman, Robert , Hawkins, Paulina , McGee, Lesley , Bentley, Stephen , Ford, Rebecca , Lehmann, Deborah
- Date: 2022
- Type: Text , Journal article
- Relation: Microbial Genomics Vol. 8, no. 7 (2022), p.
- Full Text:
- Reviewed:
- Description: Streptococcus pneumoniae is a key contributor to childhood morbidity and mortality in Papua New Guinea (PNG). For the first time, whole genome sequencing of 174 isolates has enabled detailed characterisation of diverse S. pneumoniae causing invasive disease in young children in PNG, 1989-2014. This study captures the baseline S. pneumoniae population prior to the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the national childhood immunisation programme in 2014. Relationships amongst lineages, serotypes and antimicrobial resistance traits were characterised, and the population was viewed in the context of a global collection of isolates. The analyses highlighted adiverse S. pneumoniae population associated with invasive disease in PNG, with 45 unique Global Pneumococcal Sequence Clusters (GPSCs) observed amongst the 174 isolates reflecting multiple lineages observed in PNG that have not been identified in other geographic locations. The majority of isolates were from children with meningitis, of which 52% (n=72) expressed non-PCV13 serotypes. Over a third of isolates were predicted to be resistant to at least one antimicrobial. PCV13 serotype isolates had 10.1 times the odds of being multidrug-resistant (MDR) compared to non-vaccine serotype isolates, and no isolates with GPSCs unique to PNG were MDR. Serotype 2 was the most commonly identified serotype; we identified a highly clonal cluster of serotype 2 isolates unique to PNG, and a distinct second cluster indicative of long-distance transmission. Ongoing surveillance, including whole-genome sequencing, is needed to ascertain the impact of the national PCV13 programme upon the S. pneumoniae population, including serotype replacement and antimicrobial resistance traits. © 2022 The Authors.
Cancer classification utilizing voting classifier with ensemble feature selection method and transcriptomic data
- Khatun, Rabea, Akter, Maksuda, Islam, Md Manowarul, Uddin, Md Ashraf, Talukder, Md Alamin, Kamruzzaman, Joarder, Azad, Akm, Paul, Bikash, Almoyad, Muhammad, Aryal, Sunil, Moni, Mohammad
- Authors: Khatun, Rabea , Akter, Maksuda , Islam, Md Manowarul , Uddin, Md Ashraf , Talukder, Md Alamin , Kamruzzaman, Joarder , Azad, Akm , Paul, Bikash , Almoyad, Muhammad , Aryal, Sunil , Moni, Mohammad
- Date: 2023
- Type: Text , Journal article
- Relation: Genes Vol. 14, no. 9 (2023), p.
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- Description: Biomarker-based cancer identification and classification tools are widely used in bioinformatics and machine learning fields. However, the high dimensionality of microarray gene expression data poses a challenge for identifying important genes in cancer diagnosis. Many feature selection algorithms optimize cancer diagnosis by selecting optimal features. This article proposes an ensemble rank-based feature selection method (EFSM) and an ensemble weighted average voting classifier (VT) to overcome this challenge. The EFSM uses a ranking method that aggregates features from individual selection methods to efficiently discover the most relevant and useful features. The VT combines support vector machine, k-nearest neighbor, and decision tree algorithms to create an ensemble model. The proposed method was tested on three benchmark datasets and compared to existing built-in ensemble models. The results show that our model achieved higher accuracy, with 100% for leukaemia, 94.74% for colon cancer, and 94.34% for the 11-tumor dataset. This study concludes by identifying a subset of the most important cancer-causing genes and demonstrating their significance compared to the original data. The proposed approach surpasses existing strategies in accuracy and stability, significantly impacting the development of ML-based gene analysis. It detects vital genes with higher precision and stability than other existing methods. © 2023 by the authors.
- Authors: Khatun, Rabea , Akter, Maksuda , Islam, Md Manowarul , Uddin, Md Ashraf , Talukder, Md Alamin , Kamruzzaman, Joarder , Azad, Akm , Paul, Bikash , Almoyad, Muhammad , Aryal, Sunil , Moni, Mohammad
- Date: 2023
- Type: Text , Journal article
- Relation: Genes Vol. 14, no. 9 (2023), p.
- Full Text:
- Reviewed:
- Description: Biomarker-based cancer identification and classification tools are widely used in bioinformatics and machine learning fields. However, the high dimensionality of microarray gene expression data poses a challenge for identifying important genes in cancer diagnosis. Many feature selection algorithms optimize cancer diagnosis by selecting optimal features. This article proposes an ensemble rank-based feature selection method (EFSM) and an ensemble weighted average voting classifier (VT) to overcome this challenge. The EFSM uses a ranking method that aggregates features from individual selection methods to efficiently discover the most relevant and useful features. The VT combines support vector machine, k-nearest neighbor, and decision tree algorithms to create an ensemble model. The proposed method was tested on three benchmark datasets and compared to existing built-in ensemble models. The results show that our model achieved higher accuracy, with 100% for leukaemia, 94.74% for colon cancer, and 94.34% for the 11-tumor dataset. This study concludes by identifying a subset of the most important cancer-causing genes and demonstrating their significance compared to the original data. The proposed approach surpasses existing strategies in accuracy and stability, significantly impacting the development of ML-based gene analysis. It detects vital genes with higher precision and stability than other existing methods. © 2023 by the authors.
Distinct subpopulations of DN1 thymocytes exhibit preferential gamma delta T lineage potential
- Oh, Seungyoul, Liu, Xin, Tomei, Sara, Luo, Mengxiao, Skinner, Jarrod, Berzins, Stuart, Naik, Shalin, Gray, Daniel, Chong, Mark
- Authors: Oh, Seungyoul , Liu, Xin , Tomei, Sara , Luo, Mengxiao , Skinner, Jarrod , Berzins, Stuart , Naik, Shalin , Gray, Daniel , Chong, Mark
- Date: 2023
- Type: Text , Journal article
- Relation: Frontiers in Immunology Vol. 14, no. (2023), p.
- Full Text:
- Reviewed:
- Description: The
- Authors: Oh, Seungyoul , Liu, Xin , Tomei, Sara , Luo, Mengxiao , Skinner, Jarrod , Berzins, Stuart , Naik, Shalin , Gray, Daniel , Chong, Mark
- Date: 2023
- Type: Text , Journal article
- Relation: Frontiers in Immunology Vol. 14, no. (2023), p.
- Full Text:
- Reviewed:
- Description: The
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