Doğa Eskier - Academia.edu (original) (raw)

Papers by Doğa Eskier

Research paper thumbnail of PlanTEnrichment: A How-to Guide on Rapid Identification of Transposable Elements Associated with Regions of Interest in Select Plant Genomes

Methods in molecular biology, Dec 31, 2022

Research paper thumbnail of Physicochemical differences between camelid single-domain antibodies and mammalian antibodies

Turkish Journal of Biology, Dec 27, 2023

Background/aim: In recent years, single-domain antibodies, also known as nanobodies, have emerged... more Background/aim: In recent years, single-domain antibodies, also known as nanobodies, have emerged as an alternative to full immunoglobulin Gs (IgGs), due to their various advantages, including increased solubility, faster clearance, and cheaper production. Nanobodies are generally derived from the variable domain of the camelid heavy-chain-only immunoglobulin Gs (hcIgGs). Due to the high sequence homology between variable heavy chains of camelids (V H Hs) and humans (V H s), hcIgGs are ideal candidates for nanobody development. However, further examination is needed to understand the structural differences between V H s and V H Hs. This analysis is essential for nanobody engineering to mitigate potential immunogenicity, while preserving stability, functionality, and antigen specificity. Materials and methods: We obtained the V H and V H H sequences of various camelid and non-camelid mammalian antibodies from public databases and used multiple sequence alignment based on the Chothia numbering scheme. Aligned sequences were subjected to diverse analyses encompassing paratope length, binding prediction, motif, disulfide bridge, salt bridge profiling, and physicochemical characteristic distribution. Logistic Regression coupled with the Boruta-Random Forest algorithm facilitated the comprehensive examination of physicochemical properties. Results: Our findings revealed longer, less variable paratope sequences in V H Hs, along with specific antigen binding residues with increased binding potential compared to V H s. Although the V H s showed more heterogeneous noncanonical disulfide bond patterns, the V H Hs had a higher number of noncanonical disulfide bridges. Intriguingly, a typical salt bridge between the 94th and 101st positions in the V H s had a very low encounter rate in the V H Hs. Surprisingly, we also identified notable differences in the physicochemical patterns of mostly conserved frameworks (FWs), especially the FW2 and FW3 regions, between V H s and V H Hs. Conclusion: Our findings point to possible key sites in V H Hs as candidate residues for nanobody engineering efforts.

Research paper thumbnail of In Silico Identification of Stress-Associated Transposable Elements in Arabidopsis thaliana Using Public Transcriptome Data

Methods in molecular biology, 2021

Transposable elements (TEs) have been associated with stress response in many plants, making them... more Transposable elements (TEs) have been associated with stress response in many plants, making them a key target of study. However, the high variability, genomic repeat-heavy nature, and widely noncoding character of TEs have made them difficult to study using non-specialized methods, whether experimental or computational. In this chapter, we introduce two computational workflows to analyze transposable elements using publicly available transcriptome data. In the first of these methods, we identify TEs, which show differential expression under salt stress using sample transcriptome libraries that includes noncoding transcripts. In the second, we identify protein-coding genes with differential expression under the same conditions, and determine which TEs are enriched in the promoter regions of these stress-related genes.

Research paper thumbnail of Current mutatome of SARS-CoV-2 in Turkey reveals mutations of interest

Turkish Journal of Biology, Feb 9, 2021

Introduction Coronavirus disease 2019 (COVID-19) is an ongoing pandemic, characterized by long-te... more Introduction Coronavirus disease 2019 (COVID-19) is an ongoing pandemic, characterized by long-term respiratory damage and slow onset fever, and caused by the SARS-CoV-2 betacoronavirus. The virus was first observed in human patients in late 2019, in the Wuhan province of China, and soon after showed the capacity for humanto-human transmission (Chan et al., 2020; Riou and Althaus, 2020). As of 17 August 2020 there are over 21 million confirmed cases and 767,158 recorded deaths 1. In addition to the immediately apparent symptoms, its long term effect on humans are still topics of research (

Research paper thumbnail of Transcriptome Dynamics of Human Neuronal Differentiation From iPSC

Frontiers in Cell and Developmental Biology, Dec 14, 2021

The generation and use of induced pluripotent stem cells (iPSCs) in order to obtain all different... more The generation and use of induced pluripotent stem cells (iPSCs) in order to obtain all differentiated adult cell morphologies without requiring embryonic stem cells is one of the most important discoveries in molecular biology. Among the uses of iPSCs is the generation of neuron cells and organoids to study the biological cues underlying neuronal and brain development, in addition to neurological diseases. These iPSCderived neuronal differentiation models allow us to examine the gene regulatory factors involved in such processes. Among these regulatory factors are long non-coding RNAs (lncRNAs), genes that are transcribed from the genome and have key biological functions in establishing phenotypes, but are frequently not included in studies focusing on protein coding genes. Here, we provide a comprehensive analysis and overview of the coding and non-coding transcriptome during multiple stages of the iPSC-derived neuronal differentiation process using RNA-seq. We identify previously unannotated lncRNAs via genome-guided de novo transcriptome assembly, and the distinct characteristics of the transcriptome during each stage, including differentially expressed and stage specific genes. We further identify key genes of the human neuronal differentiation network, representing novel candidates likely to have critical roles in neurogenesis using coexpression network analysis. Our findings provide a valuable resource for future studies on neuronal differentiation.

Research paper thumbnail of SARS-CoV-2 GISAID UK-US isolates (2020-09-07) genotyping VCF

VCF files containing filtered mutated sites in SARS-CoV-2 genomes obtained from GISAID EpiCoV and... more VCF files containing filtered mutated sites in SARS-CoV-2 genomes obtained from GISAID EpiCoV and submitted from the UK and the US, separated by individual mutations. The columns correspond to viral genome accession ID, nucleotide position in the genome, mutation ID (left blank in all rows), reference nucleotide, identified mutation, quality, filter, and information columns (all left blank), format (GT in all rows), column corresponding to reference genome (all 0, referring to reference nucleotide column), and columns corresponding to isolate genomes, with each row identifying the nucleotide in the POS column, and whether it is non-mutant (0), or the mutant indicated in the identified mutation column (1). The files is tab delimited, with the UK file having 12696 rows including the names, and 18135 columns, and the US file having 15588 rows including the names, and 16277 columns. The file was generated to test the hypothesis whether the different SARS-CoV-2 genes or protein coding re...

Research paper thumbnail of Transcriptome Dynamics of Human Neuronal Differentiation From iPSC

Frontiers in Cell and Developmental Biology, 2021

The generation and use of induced pluripotent stem cells (iPSCs) in order to obtain all different... more The generation and use of induced pluripotent stem cells (iPSCs) in order to obtain all differentiated adult cell morphologies without requiring embryonic stem cells is one of the most important discoveries in molecular biology. Among the uses of iPSCs is the generation of neuron cells and organoids to study the biological cues underlying neuronal and brain development, in addition to neurological diseases. These iPSC-derived neuronal differentiation models allow us to examine the gene regulatory factors involved in such processes. Among these regulatory factors are long non-coding RNAs (lncRNAs), genes that are transcribed from the genome and have key biological functions in establishing phenotypes, but are frequently not included in studies focusing on protein coding genes. Here, we provide a comprehensive analysis and overview of the coding and non-coding transcriptome during multiple stages of the iPSC-derived neuronal differentiation process using RNA-seq. We identify previousl...

Research paper thumbnail of In Silico Identification of Stress-Associated Transposable Elements in Arabidopsis thaliana Using Public Transcriptome Data

Methods in molecular biology, 2021

Transposable elements (TEs) have been associated with stress response in many plants, making them... more Transposable elements (TEs) have been associated with stress response in many plants, making them a key target of study. However, the high variability, genomic repeat-heavy nature, and widely noncoding character of TEs have made them difficult to study using non-specialized methods, whether experimental or computational. In this chapter, we introduce two computational workflows to analyze transposable elements using publicly available transcriptome data. In the first of these methods, we identify TEs, which show differential expression under salt stress using sample transcriptome libraries that includes noncoding transcripts. In the second, we identify protein-coding genes with differential expression under the same conditions, and determine which TEs are enriched in the promoter regions of these stress-related genes.

Research paper thumbnail of SARS-CoV-2 GISAID isolates (2020-06-17) genotyping VCF

VCF file containing filtered mutated sites in SARS-CoV-2 genomes obtained from GISAID EpiCoV, sep... more VCF file containing filtered mutated sites in SARS-CoV-2 genomes obtained from GISAID EpiCoV, separated by individual mutations. The columns correspond to viral genome accession ID, nucleotide position in the genome, mutation ID (left blank in all rows), reference nucleotide, identified mutation, quality, filter, and information columns (all left blank), format (GT in all rows), column corresponding to reference genome (all 0, referring to reference nucleotide column), and columns corresponding to isolate genomes, with each row identifying the nucleotide in the POS column, and whether it is non-mutant (0), or the mutant indicated in the identified mutation column (1). The file is tab delimited, with 22546 rows including the names, and 30690 columns. The file was generated to test the hypothesis whether the five most common mutations in the SARS-CoV-2 genome replication complex proteins, nsps 7, 8, 12, and 14, significantly affect the mutation density of the virus over time and whether these affect the synonymous and nonsynonymous mutation densities differently. We discovered that mutations in nsp14, an exonuclease with error correcting capabilities, are most likely to be correlated with increased mutational load across the genome compared to wildtype SARS-CoV-2. These results were obtained by identifying the frequency of mutations across all isolates in genomic regions of interest, analyzing which of the twenty mutations (five per nsp) have a statistically meaningful relationship with the mutation density in the M and E genes (chosen due to being under little selective pressure), and identifying the synonymous and nonsynonymous genomic SNV density for isolates with any of the statistically meaningful mutations, as well as isolates with none of the identified mutations.

Research paper thumbnail of Current mutatome of SARS-CoV-2 in Turkey reveals mutations of interest

TURKISH JOURNAL OF BIOLOGY, 2021

Introduction Coronavirus disease 2019 (COVID-19) is an ongoing pandemic, characterized by long-te... more Introduction Coronavirus disease 2019 (COVID-19) is an ongoing pandemic, characterized by long-term respiratory damage and slow onset fever, and caused by the SARS-CoV-2 betacoronavirus. The virus was first observed in human patients in late 2019, in the Wuhan province of China, and soon after showed the capacity for humanto-human transmission (Chan et al., 2020; Riou and Althaus, 2020). As of 17 August 2020 there are over 21 million confirmed cases and 767,158 recorded deaths 1. In addition to the immediately apparent symptoms, its long term effect on humans are still topics of research (

Research paper thumbnail of Mutation density changes in SARS-CoV-2 are related to the pandemic stage but to a lesser extent in the dominant strain with mutations in spike and RdRp

Since its emergence in Wuhan, China in late 2019, the origin and evolution of SARS-CoV-2 have bee... more Since its emergence in Wuhan, China in late 2019, the origin and evolution of SARS-CoV-2 have been among the most debated issues related to COVID-19. Throughout its spread around the world, the viral genome continued acquiring new mutations and some of them became widespread. Among them, 14408 C>T and 23403 A>G mutations in RdRp and S, respectively, became dominant in Europe and the US, which led to debates regarding their effects on the mutability and transmissibility of the virus. In this study, we aimed to investigate possible differences between time-dependent variation of mutation densities (MDe) of viral strains that carry these two mutations and those that do not. Our analyses at the genome and gene level led to two important findings: First, time-dependent changes in the average MDe of circulating SARS-CoV-2 genomes showed different characteristics before and after the beginning of April, when daily new case numbers started levelling off. Second, this pattern was much ...

Research paper thumbnail of Genes associated with T helper 17 cell differentiation and function

Frontiers in Bioscience, 2016

Interleukin-17 (IL-17)-producing T helper cells (Th17 cells) constitute a lineage of CD4 effector... more Interleukin-17 (IL-17)-producing T helper cells (Th17 cells) constitute a lineage of CD4 effector T helper cells that is distinct from the Th1 and Th2 CD4 phenotypes. In humans, Th17 differentiation is induced in the presence of the cytokines IL-1 beta, IL-6 and TGF beta, whereas IL-23 maintains Th17 survival. Effector human Th17 cells express several cytokines and cell surface markers, including IL-17A, IL-17F, IL-22, IL-26, CCR6 and TNFα. Studies on human cells have revealed that the RORC2 transcription factor plays an effective role in Th17 differentiation. Th17 cells contribute to the host immune response by involving various pathologies, including rheumatoid arthritis, multiple sclerosis and Crohn's disease. However, the full extent of their contribution to diseases is being investigated. The differentiation of Th17 cells is controlled by many transcription factors, including ROR gammat, IRF4, RUNX1, BATF, and STAT3. This review covers the general principles of CD4 T helper differentiation and the known transcription factors that play a role in the recently discovered Th17 cells.

Research paper thumbnail of SARS-CoV-2 GISAID isolates (2020 - 05 - 24) genotyping VCF by mutation

Research paper thumbnail of SARS-CoV-2 GISAID isolates (2020-05-05) genotyping VCF

Research paper thumbnail of RdRp mutations are associated with SARS-CoV-2 genome evolution

PeerJ

COVID-19, caused by the novel SARS-CoV-2 virus, started in China in late 2019, and soon became a ... more COVID-19, caused by the novel SARS-CoV-2 virus, started in China in late 2019, and soon became a global pandemic. With the help of thousands of viral genome sequences that have been accumulating, it has become possible to track the evolution of the viral genome over time as it spread across the world. An important question that still needs to be answered is whether any of the common mutations affect the viral properties, and therefore the disease characteristics. Therefore, we sought to understand the effects of mutations in RNA-dependent RNA polymerase (RdRp), particularly the common 14408C>T mutation, on mutation rate and viral spread. By focusing on mutations in the slowly evolving M or E genes, we aimed to minimize the effects of selective pressure. Our results indicate that 14408C>T mutation increases the mutation rate, while the third-most common RdRp mutation, 15324C>T, has the opposite effect. It is possible that 14408C>T mutation may have contributed to the domi...

Research paper thumbnail of Different selection dynamics of S and RdRp between SARS-CoV-2 genomes with and without the dominant mutations

Infection, Genetics and Evolution

Research paper thumbnail of Mutations of SARS-CoV-2 nsp14 exhibit strong association with increased genome-wide mutation load

SARS-CoV-2 is a betacoronavirus responsible for human cases of COVID-19, a pandemic with global i... more SARS-CoV-2 is a betacoronavirus responsible for human cases of COVID-19, a pandemic with global impact that first emerged in late 2019. Since then, the viral genome has shown considerable variance as the disease spread across the world, in part due to the zoonotic origins of the virus and the human host adaptation process. As a virus with an RNA genome that codes for its own genomic replication proteins, mutations in these proteins can significantly impact the variance rate of the genome, affecting both the survival and infection rate of the virus, and attempts at combating the disease. In this study, we analyzed the mutation densities of viral isolates carrying frequently observed mutations for four proteins in the RNA synthesis complex over time in comparison to wildtype isolates. Our observations suggest mutations in nsp14, an error-correcting exonuclease protein, have the strongest association with increased mutation load in both regions without selective pressure and across the...

Research paper thumbnail of PlanTEnrichment: A How-to Guide on Rapid Identification of Transposable Elements Associated with Regions of Interest in Select Plant Genomes

Methods in molecular biology, Dec 31, 2022

Research paper thumbnail of Physicochemical differences between camelid single-domain antibodies and mammalian antibodies

Turkish Journal of Biology, Dec 27, 2023

Background/aim: In recent years, single-domain antibodies, also known as nanobodies, have emerged... more Background/aim: In recent years, single-domain antibodies, also known as nanobodies, have emerged as an alternative to full immunoglobulin Gs (IgGs), due to their various advantages, including increased solubility, faster clearance, and cheaper production. Nanobodies are generally derived from the variable domain of the camelid heavy-chain-only immunoglobulin Gs (hcIgGs). Due to the high sequence homology between variable heavy chains of camelids (V H Hs) and humans (V H s), hcIgGs are ideal candidates for nanobody development. However, further examination is needed to understand the structural differences between V H s and V H Hs. This analysis is essential for nanobody engineering to mitigate potential immunogenicity, while preserving stability, functionality, and antigen specificity. Materials and methods: We obtained the V H and V H H sequences of various camelid and non-camelid mammalian antibodies from public databases and used multiple sequence alignment based on the Chothia numbering scheme. Aligned sequences were subjected to diverse analyses encompassing paratope length, binding prediction, motif, disulfide bridge, salt bridge profiling, and physicochemical characteristic distribution. Logistic Regression coupled with the Boruta-Random Forest algorithm facilitated the comprehensive examination of physicochemical properties. Results: Our findings revealed longer, less variable paratope sequences in V H Hs, along with specific antigen binding residues with increased binding potential compared to V H s. Although the V H s showed more heterogeneous noncanonical disulfide bond patterns, the V H Hs had a higher number of noncanonical disulfide bridges. Intriguingly, a typical salt bridge between the 94th and 101st positions in the V H s had a very low encounter rate in the V H Hs. Surprisingly, we also identified notable differences in the physicochemical patterns of mostly conserved frameworks (FWs), especially the FW2 and FW3 regions, between V H s and V H Hs. Conclusion: Our findings point to possible key sites in V H Hs as candidate residues for nanobody engineering efforts.

Research paper thumbnail of In Silico Identification of Stress-Associated Transposable Elements in Arabidopsis thaliana Using Public Transcriptome Data

Methods in molecular biology, 2021

Transposable elements (TEs) have been associated with stress response in many plants, making them... more Transposable elements (TEs) have been associated with stress response in many plants, making them a key target of study. However, the high variability, genomic repeat-heavy nature, and widely noncoding character of TEs have made them difficult to study using non-specialized methods, whether experimental or computational. In this chapter, we introduce two computational workflows to analyze transposable elements using publicly available transcriptome data. In the first of these methods, we identify TEs, which show differential expression under salt stress using sample transcriptome libraries that includes noncoding transcripts. In the second, we identify protein-coding genes with differential expression under the same conditions, and determine which TEs are enriched in the promoter regions of these stress-related genes.

Research paper thumbnail of Current mutatome of SARS-CoV-2 in Turkey reveals mutations of interest

Turkish Journal of Biology, Feb 9, 2021

Introduction Coronavirus disease 2019 (COVID-19) is an ongoing pandemic, characterized by long-te... more Introduction Coronavirus disease 2019 (COVID-19) is an ongoing pandemic, characterized by long-term respiratory damage and slow onset fever, and caused by the SARS-CoV-2 betacoronavirus. The virus was first observed in human patients in late 2019, in the Wuhan province of China, and soon after showed the capacity for humanto-human transmission (Chan et al., 2020; Riou and Althaus, 2020). As of 17 August 2020 there are over 21 million confirmed cases and 767,158 recorded deaths 1. In addition to the immediately apparent symptoms, its long term effect on humans are still topics of research (

Research paper thumbnail of Transcriptome Dynamics of Human Neuronal Differentiation From iPSC

Frontiers in Cell and Developmental Biology, Dec 14, 2021

The generation and use of induced pluripotent stem cells (iPSCs) in order to obtain all different... more The generation and use of induced pluripotent stem cells (iPSCs) in order to obtain all differentiated adult cell morphologies without requiring embryonic stem cells is one of the most important discoveries in molecular biology. Among the uses of iPSCs is the generation of neuron cells and organoids to study the biological cues underlying neuronal and brain development, in addition to neurological diseases. These iPSCderived neuronal differentiation models allow us to examine the gene regulatory factors involved in such processes. Among these regulatory factors are long non-coding RNAs (lncRNAs), genes that are transcribed from the genome and have key biological functions in establishing phenotypes, but are frequently not included in studies focusing on protein coding genes. Here, we provide a comprehensive analysis and overview of the coding and non-coding transcriptome during multiple stages of the iPSC-derived neuronal differentiation process using RNA-seq. We identify previously unannotated lncRNAs via genome-guided de novo transcriptome assembly, and the distinct characteristics of the transcriptome during each stage, including differentially expressed and stage specific genes. We further identify key genes of the human neuronal differentiation network, representing novel candidates likely to have critical roles in neurogenesis using coexpression network analysis. Our findings provide a valuable resource for future studies on neuronal differentiation.

Research paper thumbnail of SARS-CoV-2 GISAID UK-US isolates (2020-09-07) genotyping VCF

VCF files containing filtered mutated sites in SARS-CoV-2 genomes obtained from GISAID EpiCoV and... more VCF files containing filtered mutated sites in SARS-CoV-2 genomes obtained from GISAID EpiCoV and submitted from the UK and the US, separated by individual mutations. The columns correspond to viral genome accession ID, nucleotide position in the genome, mutation ID (left blank in all rows), reference nucleotide, identified mutation, quality, filter, and information columns (all left blank), format (GT in all rows), column corresponding to reference genome (all 0, referring to reference nucleotide column), and columns corresponding to isolate genomes, with each row identifying the nucleotide in the POS column, and whether it is non-mutant (0), or the mutant indicated in the identified mutation column (1). The files is tab delimited, with the UK file having 12696 rows including the names, and 18135 columns, and the US file having 15588 rows including the names, and 16277 columns. The file was generated to test the hypothesis whether the different SARS-CoV-2 genes or protein coding re...

Research paper thumbnail of Transcriptome Dynamics of Human Neuronal Differentiation From iPSC

Frontiers in Cell and Developmental Biology, 2021

The generation and use of induced pluripotent stem cells (iPSCs) in order to obtain all different... more The generation and use of induced pluripotent stem cells (iPSCs) in order to obtain all differentiated adult cell morphologies without requiring embryonic stem cells is one of the most important discoveries in molecular biology. Among the uses of iPSCs is the generation of neuron cells and organoids to study the biological cues underlying neuronal and brain development, in addition to neurological diseases. These iPSC-derived neuronal differentiation models allow us to examine the gene regulatory factors involved in such processes. Among these regulatory factors are long non-coding RNAs (lncRNAs), genes that are transcribed from the genome and have key biological functions in establishing phenotypes, but are frequently not included in studies focusing on protein coding genes. Here, we provide a comprehensive analysis and overview of the coding and non-coding transcriptome during multiple stages of the iPSC-derived neuronal differentiation process using RNA-seq. We identify previousl...

Research paper thumbnail of In Silico Identification of Stress-Associated Transposable Elements in Arabidopsis thaliana Using Public Transcriptome Data

Methods in molecular biology, 2021

Transposable elements (TEs) have been associated with stress response in many plants, making them... more Transposable elements (TEs) have been associated with stress response in many plants, making them a key target of study. However, the high variability, genomic repeat-heavy nature, and widely noncoding character of TEs have made them difficult to study using non-specialized methods, whether experimental or computational. In this chapter, we introduce two computational workflows to analyze transposable elements using publicly available transcriptome data. In the first of these methods, we identify TEs, which show differential expression under salt stress using sample transcriptome libraries that includes noncoding transcripts. In the second, we identify protein-coding genes with differential expression under the same conditions, and determine which TEs are enriched in the promoter regions of these stress-related genes.

Research paper thumbnail of SARS-CoV-2 GISAID isolates (2020-06-17) genotyping VCF

VCF file containing filtered mutated sites in SARS-CoV-2 genomes obtained from GISAID EpiCoV, sep... more VCF file containing filtered mutated sites in SARS-CoV-2 genomes obtained from GISAID EpiCoV, separated by individual mutations. The columns correspond to viral genome accession ID, nucleotide position in the genome, mutation ID (left blank in all rows), reference nucleotide, identified mutation, quality, filter, and information columns (all left blank), format (GT in all rows), column corresponding to reference genome (all 0, referring to reference nucleotide column), and columns corresponding to isolate genomes, with each row identifying the nucleotide in the POS column, and whether it is non-mutant (0), or the mutant indicated in the identified mutation column (1). The file is tab delimited, with 22546 rows including the names, and 30690 columns. The file was generated to test the hypothesis whether the five most common mutations in the SARS-CoV-2 genome replication complex proteins, nsps 7, 8, 12, and 14, significantly affect the mutation density of the virus over time and whether these affect the synonymous and nonsynonymous mutation densities differently. We discovered that mutations in nsp14, an exonuclease with error correcting capabilities, are most likely to be correlated with increased mutational load across the genome compared to wildtype SARS-CoV-2. These results were obtained by identifying the frequency of mutations across all isolates in genomic regions of interest, analyzing which of the twenty mutations (five per nsp) have a statistically meaningful relationship with the mutation density in the M and E genes (chosen due to being under little selective pressure), and identifying the synonymous and nonsynonymous genomic SNV density for isolates with any of the statistically meaningful mutations, as well as isolates with none of the identified mutations.

Research paper thumbnail of Current mutatome of SARS-CoV-2 in Turkey reveals mutations of interest

TURKISH JOURNAL OF BIOLOGY, 2021

Introduction Coronavirus disease 2019 (COVID-19) is an ongoing pandemic, characterized by long-te... more Introduction Coronavirus disease 2019 (COVID-19) is an ongoing pandemic, characterized by long-term respiratory damage and slow onset fever, and caused by the SARS-CoV-2 betacoronavirus. The virus was first observed in human patients in late 2019, in the Wuhan province of China, and soon after showed the capacity for humanto-human transmission (Chan et al., 2020; Riou and Althaus, 2020). As of 17 August 2020 there are over 21 million confirmed cases and 767,158 recorded deaths 1. In addition to the immediately apparent symptoms, its long term effect on humans are still topics of research (

Research paper thumbnail of Mutation density changes in SARS-CoV-2 are related to the pandemic stage but to a lesser extent in the dominant strain with mutations in spike and RdRp

Since its emergence in Wuhan, China in late 2019, the origin and evolution of SARS-CoV-2 have bee... more Since its emergence in Wuhan, China in late 2019, the origin and evolution of SARS-CoV-2 have been among the most debated issues related to COVID-19. Throughout its spread around the world, the viral genome continued acquiring new mutations and some of them became widespread. Among them, 14408 C>T and 23403 A>G mutations in RdRp and S, respectively, became dominant in Europe and the US, which led to debates regarding their effects on the mutability and transmissibility of the virus. In this study, we aimed to investigate possible differences between time-dependent variation of mutation densities (MDe) of viral strains that carry these two mutations and those that do not. Our analyses at the genome and gene level led to two important findings: First, time-dependent changes in the average MDe of circulating SARS-CoV-2 genomes showed different characteristics before and after the beginning of April, when daily new case numbers started levelling off. Second, this pattern was much ...

Research paper thumbnail of Genes associated with T helper 17 cell differentiation and function

Frontiers in Bioscience, 2016

Interleukin-17 (IL-17)-producing T helper cells (Th17 cells) constitute a lineage of CD4 effector... more Interleukin-17 (IL-17)-producing T helper cells (Th17 cells) constitute a lineage of CD4 effector T helper cells that is distinct from the Th1 and Th2 CD4 phenotypes. In humans, Th17 differentiation is induced in the presence of the cytokines IL-1 beta, IL-6 and TGF beta, whereas IL-23 maintains Th17 survival. Effector human Th17 cells express several cytokines and cell surface markers, including IL-17A, IL-17F, IL-22, IL-26, CCR6 and TNFα. Studies on human cells have revealed that the RORC2 transcription factor plays an effective role in Th17 differentiation. Th17 cells contribute to the host immune response by involving various pathologies, including rheumatoid arthritis, multiple sclerosis and Crohn's disease. However, the full extent of their contribution to diseases is being investigated. The differentiation of Th17 cells is controlled by many transcription factors, including ROR gammat, IRF4, RUNX1, BATF, and STAT3. This review covers the general principles of CD4 T helper differentiation and the known transcription factors that play a role in the recently discovered Th17 cells.

Research paper thumbnail of SARS-CoV-2 GISAID isolates (2020 - 05 - 24) genotyping VCF by mutation

Research paper thumbnail of SARS-CoV-2 GISAID isolates (2020-05-05) genotyping VCF

Research paper thumbnail of RdRp mutations are associated with SARS-CoV-2 genome evolution

PeerJ

COVID-19, caused by the novel SARS-CoV-2 virus, started in China in late 2019, and soon became a ... more COVID-19, caused by the novel SARS-CoV-2 virus, started in China in late 2019, and soon became a global pandemic. With the help of thousands of viral genome sequences that have been accumulating, it has become possible to track the evolution of the viral genome over time as it spread across the world. An important question that still needs to be answered is whether any of the common mutations affect the viral properties, and therefore the disease characteristics. Therefore, we sought to understand the effects of mutations in RNA-dependent RNA polymerase (RdRp), particularly the common 14408C>T mutation, on mutation rate and viral spread. By focusing on mutations in the slowly evolving M or E genes, we aimed to minimize the effects of selective pressure. Our results indicate that 14408C>T mutation increases the mutation rate, while the third-most common RdRp mutation, 15324C>T, has the opposite effect. It is possible that 14408C>T mutation may have contributed to the domi...

Research paper thumbnail of Different selection dynamics of S and RdRp between SARS-CoV-2 genomes with and without the dominant mutations

Infection, Genetics and Evolution

Research paper thumbnail of Mutations of SARS-CoV-2 nsp14 exhibit strong association with increased genome-wide mutation load

SARS-CoV-2 is a betacoronavirus responsible for human cases of COVID-19, a pandemic with global i... more SARS-CoV-2 is a betacoronavirus responsible for human cases of COVID-19, a pandemic with global impact that first emerged in late 2019. Since then, the viral genome has shown considerable variance as the disease spread across the world, in part due to the zoonotic origins of the virus and the human host adaptation process. As a virus with an RNA genome that codes for its own genomic replication proteins, mutations in these proteins can significantly impact the variance rate of the genome, affecting both the survival and infection rate of the virus, and attempts at combating the disease. In this study, we analyzed the mutation densities of viral isolates carrying frequently observed mutations for four proteins in the RNA synthesis complex over time in comparison to wildtype isolates. Our observations suggest mutations in nsp14, an error-correcting exonuclease protein, have the strongest association with increased mutation load in both regions without selective pressure and across the...