E-Mail: akash.srivastava@uni-jena.de
Room: FLI 2.042
Phone: +49 3641 65-6828
Publications
2022
Fuesslin, Valeria; Krautwurst, Sebastian; Srivastava, Akash; Winter, Doris; Liedigk, Britta; Thye, Thorsten; Herrera-León, Silvia; Wohl, Shirlee; May, Jürgen; Fobil, Julius N.; Eibach, Daniel; Marz, Manja; Schuldt, Kathrin
In: Front Microbiol, vol. 13, pp. 909692, 2022.
@article{Fuesslin2022,
title = {Prediction of Antibiotic Susceptibility Profiles of \textit{Vibrio cholerae} Isolates From Whole Genome Illumina and Nanopore Sequencing Data: CholerAegon},
author = {Valeria Fuesslin and Sebastian Krautwurst and Akash Srivastava and Doris Winter and Britta Liedigk and Thorsten Thye and Silvia Herrera-León and Shirlee Wohl and Jürgen May and Julius N. Fobil and Daniel Eibach and Manja Marz and Kathrin Schuldt},
url = {https://github.com/RaverJay/CholerAegon },
doi = {10.3389/fmicb.2022.909692},
year = {2022},
date = {2022-06-22},
journal = {Front Microbiol},
volume = {13},
pages = {909692},
abstract = {During the last decades, antimicrobial resistance (AMR) has become a global public health concern. Nowadays multi-drug resistance is commonly observed in strains of Vibrio cholerae, the etiological agent of cholera. In order to limit the spread of pathogenic drug-resistant bacteria and to maintain treatment options the analysis of clinical samples and their AMR profiles are essential. Particularly, in low-resource settings a timely analysis of AMR profiles is often impaired due to lengthy culturing procedures for antibiotic susceptibility testing or lack of laboratory capacity. In this study, we explore the applicability of whole genome sequencing for the prediction of AMR profiles of V. cholerae. We developed the pipeline CholerAegon for the in silico prediction of AMR profiles of 82 V. cholerae genomes assembled from long and short sequencing reads. By correlating the predicted profiles with results from phenotypic antibiotic susceptibility testing we show that the prediction can replace in vitro susceptibility testing for five of seven antibiotics. Because of the relatively low costs, possibility for real-time data analyses, and portability, the Oxford Nanopore Technologies MinION sequencing platform—especially in light of an upcoming less error-prone technology for the platform—appears to be well suited for pathogen genomic analyses such as the one described here. Together with CholerAegon, it can leverage pathogen genomics to improve disease surveillance and to control further spread of antimicrobial resistance.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
During the last decades, antimicrobial resistance (AMR) has become a global public health concern. Nowadays multi-drug resistance is commonly observed in strains of Vibrio cholerae, the etiological agent of cholera. In order to limit the spread of pathogenic drug-resistant bacteria and to maintain treatment options the analysis of clinical samples and their AMR profiles are essential. Particularly, in low-resource settings a timely analysis of AMR profiles is often impaired due to lengthy culturing procedures for antibiotic susceptibility testing or lack of laboratory capacity. In this study, we explore the applicability of whole genome sequencing for the prediction of AMR profiles of V. cholerae. We developed the pipeline CholerAegon for the in silico prediction of AMR profiles of 82 V. cholerae genomes assembled from long and short sequencing reads. By correlating the predicted profiles with results from phenotypic antibiotic susceptibility testing we show that the prediction can replace in vitro susceptibility testing for five of seven antibiotics. Because of the relatively low costs, possibility for real-time data analyses, and portability, the Oxford Nanopore Technologies MinION sequencing platform—especially in light of an upcoming less error-prone technology for the platform—appears to be well suited for pathogen genomic analyses such as the one described here. Together with CholerAegon, it can leverage pathogen genomics to improve disease surveillance and to control further spread of antimicrobial resistance.
Barth, Emanuel; Burggraaff, Johannes; Srivastava, Akash; Winckler, Thomas
Nanopore sequencing for mapping of retrotransposon integration sites in the Dictyostelium discoideum genome Journal Article
In: MicroPubl Biol, 2022.
@article{nokey,
title = {Nanopore sequencing for mapping of retrotransposon integration sites in the \textit{Dictyostelium discoideum} genome},
author = {Emanuel Barth and Johannes Burggraaff and Akash Srivastava and Thomas Winckler
},
doi = {10.17912/micropub.biology.000543},
year = {2022},
date = {2022-03-18},
journal = {MicroPubl Biol},
abstract = {The unicellular eukaryote \textit{Dictyostelium discoideum} has a gene-dense haploid genome. This configuration presents mobile elements with the particular challenge of replicating without causing excessive damage to the host through insertional mutagenesis or recombination between repetitive sequences. \textit{D. discoideum} harbors an active population of the retrotransposon TRE5-A that integrates in a narrow window of ~50 bp upstream of tRNA genes. We assume that this integration preference was developed to avoid the disruption of protein-coding genes. Therefore, we recently mapped new integrations of a genetically tagged TRE5-A element at tRNA genes using PCR-based enrichment of integration junctions. However, the PCR-based enrichment produced several artificial DNA fusions that prevented the mapping of integration sites in unknown places of the genome. Here, we reanalyzed the previous experiment using nanopore sequencing. We summarize the advantages and limitations of direct genome resequencing for the mapping of mobile element integrations.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The unicellular eukaryote Dictyostelium discoideum has a gene-dense haploid genome. This configuration presents mobile elements with the particular challenge of replicating without causing excessive damage to the host through insertional mutagenesis or recombination between repetitive sequences. D. discoideum harbors an active population of the retrotransposon TRE5-A that integrates in a narrow window of ~50 bp upstream of tRNA genes. We assume that this integration preference was developed to avoid the disruption of protein-coding genes. Therefore, we recently mapped new integrations of a genetically tagged TRE5-A element at tRNA genes using PCR-based enrichment of integration junctions. However, the PCR-based enrichment produced several artificial DNA fusions that prevented the mapping of integration sites in unknown places of the genome. Here, we reanalyzed the previous experiment using nanopore sequencing. We summarize the advantages and limitations of direct genome resequencing for the mapping of mobile element integrations.
2021
Barth, Emanuel; Srivastava, Akash; Wengerodt, Diane; Stojiljkovic, Milan; Axer, Hubertus; Witte, Otto W; Kretz, Alexandra; Marz, Manja
Age-dependent expression changes of circadian system-related genes reveal a potentially conserved link to aging Journal Article
In: Aging, vol. 13, no. 24, pp. 25694-25716, 2021.
@article{nokey,
title = {Age-dependent expression changes of circadian system-related genes reveal a potentially conserved link to aging},
author = {Emanuel Barth and Akash Srivastava and Diane Wengerodt and Milan Stojiljkovic and Hubertus Axer and Otto W Witte and Alexandra Kretz and Manja Marz
},
doi = {10.18632/aging.203788},
year = {2021},
date = {2021-12-19},
journal = {Aging},
volume = {13},
number = {24},
pages = {25694-25716},
abstract = {The circadian clock system influences the biology of life by establishing circadian rhythms in organisms, tissues, and cells, thus regulating essential biological processes based on the day/night cycle. Circadian rhythms change over a lifetime due to maturation and aging, and disturbances in the control of the circadian system are associated with several age-related pathologies. However, the impact of chronobiology and the circadian system on healthy organ and tissue aging remains largely unknown. Whether aging-related changes of the circadian system's regulation follow a conserved pattern across different species and tissues, hence representing a common driving force of aging, is unclear. Based on a cross-sectional transcriptome analysis covering 329 RNA-Seq libraries, we provide indications that the circadian system is subjected to aging-related gene alterations shared between evolutionarily distinct species, such as Homo sapiens, Mus musculus, Danio rerio, and Nothobranchius furzeri. We discovered differentially expressed genes by comparing tissue-specific transcriptional profiles of mature, aged, and old-age individuals and report on six genes (per2, dec2, cirp, klf10, nfil3, and dbp) of the circadian system, which show conserved aging-related expression patterns in four organs of the species examined. Our results illustrate how the circadian system and aging might influence each other in various tissues over a long lifespan and conceptually complement previous studies tracking short-term diurnal and nocturnal gene expression oscillations.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The circadian clock system influences the biology of life by establishing circadian rhythms in organisms, tissues, and cells, thus regulating essential biological processes based on the day/night cycle. Circadian rhythms change over a lifetime due to maturation and aging, and disturbances in the control of the circadian system are associated with several age-related pathologies. However, the impact of chronobiology and the circadian system on healthy organ and tissue aging remains largely unknown. Whether aging-related changes of the circadian system's regulation follow a conserved pattern across different species and tissues, hence representing a common driving force of aging, is unclear. Based on a cross-sectional transcriptome analysis covering 329 RNA-Seq libraries, we provide indications that the circadian system is subjected to aging-related gene alterations shared between evolutionarily distinct species, such as Homo sapiens, Mus musculus, Danio rerio, and Nothobranchius furzeri. We discovered differentially expressed genes by comparing tissue-specific transcriptional profiles of mature, aged, and old-age individuals and report on six genes (per2, dec2, cirp, klf10, nfil3, and dbp) of the circadian system, which show conserved aging-related expression patterns in four organs of the species examined. Our results illustrate how the circadian system and aging might influence each other in various tissues over a long lifespan and conceptually complement previous studies tracking short-term diurnal and nocturnal gene expression oscillations.
2020
Srivastava, Akash; Barth, Emanuel; Ermolaeva, Maria A.; Guenther, Madlen; Frahm, Christiane; Marz, Manja; Witte, Otto W.
Tissue-specific Gene Expression Changes Are Associated with Aging in Mice Journal Article
In: Genomics Proteomics Bioinformatics, vol. 18, no. 4, pp. 430–442, 2020.
@article{Srivastava:20,
title = {Tissue-specific Gene Expression Changes Are Associated with Aging in Mice},
author = {Akash Srivastava and Emanuel Barth and Maria A. Ermolaeva and Madlen Guenther and Christiane Frahm and Manja Marz and Otto W. Witte},
doi = {10.1016/j.gpb.2020.12.001},
year = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Genomics Proteomics Bioinformatics},
volume = {18},
number = {4},
pages = {430--442},
publisher = {Elsevier BV},
abstract = {Aging is a complex process that can be characterized by functional and cognitive decline in an individual. Aging can be assessed based on the functional capacity of vital organs and their intricate interactions with one another. Thus, the nature of aging can be described by focusing on a specific organ and an individual itself. However, to fully understand the complexity of aging, one must investigate not only a single tissue or biological process but also its complex interplay and interdependencies with other biological processes. Here, using RNA-seq, we monitored changes in the transcriptome during aging in four tissues (including brain, blood, skin and liver) in mice at 9 months, 15 months, and 24 months, with a final evaluation at the very old age of 30 months. We identified several genes and processes that were differentially regulated during aging in both tissue-dependent and tissue-independent manners. Most importantly, we found that the electron transport chain (ETC) of mitochondria was similarly affected at the transcriptome level in the four tissues during the aging process. We also identified the liver as the tissue showing the largest variety of differentially expressed genes (DEGs) over time. Lcn2 (Lipocalin-2) was found to be similarly regulated among all tissues, and its effect on longevity and survival was validated using its orthologue in Caenorhabditis elegans. Our study demonstrated that the molecular processes of aging are relatively subtle in their progress, and the aging process of every tissue depends on the tissue’s specialized function and environment. Hence, individual gene or process alone cannot be described as the key of aging in the whole organism.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Aging is a complex process that can be characterized by functional and cognitive decline in an individual. Aging can be assessed based on the functional capacity of vital organs and their intricate interactions with one another. Thus, the nature of aging can be described by focusing on a specific organ and an individual itself. However, to fully understand the complexity of aging, one must investigate not only a single tissue or biological process but also its complex interplay and interdependencies with other biological processes. Here, using RNA-seq, we monitored changes in the transcriptome during aging in four tissues (including brain, blood, skin and liver) in mice at 9 months, 15 months, and 24 months, with a final evaluation at the very old age of 30 months. We identified several genes and processes that were differentially regulated during aging in both tissue-dependent and tissue-independent manners. Most importantly, we found that the electron transport chain (ETC) of mitochondria was similarly affected at the transcriptome level in the four tissues during the aging process. We also identified the liver as the tissue showing the largest variety of differentially expressed genes (DEGs) over time. Lcn2 (Lipocalin-2) was found to be similarly regulated among all tissues, and its effect on longevity and survival was validated using its orthologue in Caenorhabditis elegans. Our study demonstrated that the molecular processes of aging are relatively subtle in their progress, and the aging process of every tissue depends on the tissue’s specialized function and environment. Hence, individual gene or process alone cannot be described as the key of aging in the whole organism.
2019
Srivastava, Akash
2019.
@phdthesis{nokey,
title = {Whole-transcriptome changes in gene expression in multiple tissues across various organisms during aging},
author = {Akash Srivastava},
url = {https://suche.thulb.uni-jena.de/Record/1679045660},
year = {2019},
date = {2019-08-27},
urldate = {2019-01-01},
howpublished = {Friedrich-Schiller-Universität Jena},
keywords = {},
pubstate = {published},
tppubtype = {phdthesis}
}
Barth, Emanuel; Srivastava, Akash; Stojiljkovic, Milan; Frahm, Christiane; Axer, Hubertus; Witte, Otto W; Marz, Manja
Conserved aging-related signatures of senescence and inflammation in different tissues and species. Journal Article
In: Aging, vol. 11, no. 19, pp. 8556—8572, 2019.
@article{Barth:19,
title = {Conserved aging-related signatures of senescence and inflammation in different tissues and species.},
author = {Emanuel Barth and Akash Srivastava and Milan Stojiljkovic and Christiane Frahm and Hubertus Axer and Otto W Witte and Manja Marz},
doi = {10.18632/aging.102345},
year = {2019},
date = {2019-02-26},
urldate = {2019-02-26},
journal = {Aging},
volume = {11},
number = {19},
pages = {8556—8572},
abstract = {Increasing evidence indicates that chronic inflammation and senescence are the cause of many severe age-related diseases, with both biological processes highly upregulated during aging. However, until now, it has remained unknown whether specific inflammation- or senescence-related genes exist that are common between different species or tissues. These potential markers of aging could help to identify possible targets for therapeutic interventions of aging-associated afflictions and might also deepen our understanding of the principal mechanisms of aging. With the objective of identifying such signatures of aging and tissue-specific aging markers, we analyzed a multitude of cross-sectional RNA-Seq data from four evolutionarily distinct species (human, mouse and two fish) and four different tissues (blood, brain, liver and skin). In at least three different species and three different tissues, we identified several genes that displayed similar expression patterns that might serve as potential aging markers. Additionally, we show that genes involved in aging-related processes tend to be tighter controlled in long-lived than in average-lived individuals. These observations hint at a general genetic level that affect an individual's life span. Altogether, this descriptive study contributes to a better understanding of common aging signatures as well as tissue-specific aging patterns and supplies the basis for further investigative age-related studies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Increasing evidence indicates that chronic inflammation and senescence are the cause of many severe age-related diseases, with both biological processes highly upregulated during aging. However, until now, it has remained unknown whether specific inflammation- or senescence-related genes exist that are common between different species or tissues. These potential markers of aging could help to identify possible targets for therapeutic interventions of aging-associated afflictions and might also deepen our understanding of the principal mechanisms of aging. With the objective of identifying such signatures of aging and tissue-specific aging markers, we analyzed a multitude of cross-sectional RNA-Seq data from four evolutionarily distinct species (human, mouse and two fish) and four different tissues (blood, brain, liver and skin). In at least three different species and three different tissues, we identified several genes that displayed similar expression patterns that might serve as potential aging markers. Additionally, we show that genes involved in aging-related processes tend to be tighter controlled in long-lived than in average-lived individuals. These observations hint at a general genetic level that affect an individual's life span. Altogether, this descriptive study contributes to a better understanding of common aging signatures as well as tissue-specific aging patterns and supplies the basis for further investigative age-related studies.