Ontology highlight
ABSTRACT:
PROVIDER: PRJNA565437 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10119311_1.fastq.gz | Fastqsanger.gz | |||
| SRR10119311_2.fastq.gz | Fastqsanger.gz | |||
| SRR10119312_1.fastq.gz | Fastqsanger.gz | |||
| SRR10119312_2.fastq.gz | Fastqsanger.gz | |||
| SRR10119313_1.fastq.gz | Fastqsanger.gz |
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Project description:Collateral fitness effects of mutations
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Project description:We found that several variants with 2-4 mutations on Higher Eukaryotes and Prokaryotes Nucleotide-binding (HEPN) domains showed undiminished on-target activity but markedly reduced collateral effects. Furthermore, transcriptome-wide off-target effects and cell growth arrest induced by wild-type Cas13d were found to be absent for a Cas13d variant. Thus, high-fidelity Cas13 variants with minimal collateral effects are now available for the targeted degradation of RNAs in basic research and therapeutic applications.
2022-06-28 | GSE168246 | GEO
Project description:In adaptive evolution, an increase in fitness to an environment is frequently accompanied by changes in fitness to other environmental conditions, called cross-resistance and sensitivity. Although the networks between fitness changes affect the course of evolution substantially, the mechanisms underlying such fitness changes are yet to be fully elucidated. Herein, we performed high-throughput laboratory evolution of Escherichia coli under various stress conditions using an automated culture system, and quantified how the acquisition of resistance to one stressor alters the resistance to other stressors. We demonstrated that resistance changes could be quantitatively predicted based on changes in the transcriptome of the resistant strains. We also identified several genes and gene functions, for which mutations were commonly fixed in the strains resistant to the same stress, which could partially explain the observed cross-resistance and collateral sensitivity. The integration of transcriptome and genome data enabled us to clarify the bacterial stress resistance mechanisms.
2017-10-17 | GSE89746 | GEO
Project description:Aneuploidy is a hallmark of tumor cells, and yet the precise relationship between aneuploidy and a cell’s proliferative ability, or cellular fitness, has remained elusive. In this study, we have combined a detailed analysis of aneuploid clones isolated from laboratory-evolved populations of Saccharomyces cerevisiae with a systematic, genome-wide screen for the fitness effects of telomeric amplifications to address the relationship between aneuploidy and cellular fitness. We found that aneuploid clones rise to high population frequencies in nutrient-limited evolution experiments and show increased fitness relative to wild type. Direct competition experiments confirmed that three out of four aneuploid events isolated from evolved populations were themselves sufficient to improve fitness. To expand the scope beyond this small number of exemplars, we created a genome-wide collection of >1,800 diploid yeast strains, each containing a different telomeric amplicon (Tamp), ranging in size from 0.4 to 1,000 kb. Using pooled competition experiments in nutrient-limited chemostats followed by high-throughput sequencing of strain-identifying barcodes, we determined the fitness effects of these >1,800 Tamps under three different conditions. Our data revealed that the fitness landscape explored by telomeric amplifications is much broader than that explored by single-gene amplifications. As also observed in the evolved clones, we found the fitness effects of most Tamps to be condition specific, with a minority showing common effects in all three conditions. By integrating our data with previous work that examined the fitness effects of single-gene amplifications genome-wide, we found that a small number of genes within each Tamp are centrally responsible for each Tamp’s fitness effects. Our genome-wide Tamp screen confirmed that telomeric amplifications identified in laboratory-evolved populations generally increased fitness. Our results show that Tamps are mutations that produce large, typically condition-dependent changes in fitness that are important drivers of increased fitness in asexually evolving populations.
2015-04-12 | GSE67769 | GEO
Project description:High-throughput sequencing has enabled genetic screens that can rapidly identify mutations that occur during experimental evolution. The presence of a mutation in an evolved lineage does not, however, constitute proof that the mutation is adaptive, given the well-known and widespread phenomenon of genetic hitchhiking, in which a non-adaptive or even detrimental mutation can co-occur in a genome with a beneficial mutation and the combined genotype is carried to high frequency by selection. We approximated the spectrum of possible beneficial mutations in Saccharomyces cerevisiae using sets of single-gene deletions and amplifications of almost all the genes in the S. cerevisiae genome. We determined the fitness effects of each mutation in three different nutrient-limited conditions using pooled competitions followed by barcode sequencing. Although most of the mutations were neutral or deleterious, ~500 of them increased fitness. We then compared those results to the mutations that actually occurred during experimental evolution in the same three nutrient-limited conditions. On average, ~35% of the mutations that occurred during experimental evolution were predicted by the systematic screen to be beneficial. We found that the distribution of fitness effects depended on the selective conditions. In the phosphate-limited and glucose-limited conditions, a large number of beneficial mutations of nearly equivalent, small effects drove the fitness increases. In the sulfate-limited condition, one type of mutation, the amplification of the high-affinity sulfate transporter, dominated. In the absence of that mutation, evolution in the sulfate-limited condition involved mutations in other genes that were not observed previously—but were predicted by the systematic screen. Thus, gross functional screens have the potential to predict and identify adaptive mutations that occur during experimental evolution. Previously version available on bioRXiv.
2015-01-01 | GSE58497 | GEO
Project description:The prevalence of clonal haematopoiesis of indeterminate potential (CHIP) in healthy individuals increases rapidly from age 60 onwards and has been associated with increased risk for malignancy, heart disease and ischemic stroke. CHIP is driven by somatic mutations in stem cells that are also drivers of myeloid malignancies. Since mutations in stem cells often drive leukaemia, we hypothesised that stem cell fitness substantially contributes to transformation from CHIP to leukaemia. Stem cell fitness is defined as the proliferative advantage over cells carrying no or only neutral mutations. It is currently unknown whether mutations in different CHIP genes lead to distinct fitness advantages that could form the basis for patient stratification. We set out to quantify the fitness effects of CHIP drivers over a 12-year timespan in older age, using longitudinal error-corrected sequencing data. Two key results support the possibility for individualised clinical monitoring of CHIP: (i) We developed a new filtering method to extract fitness effects from longitudinal data using Bayesian inference, while taking into account individual mutational context and co-occurrence of mutations, and thus quantify the growth potential of variants within each individual. (ii) We show that gene-specific fitness differences can outweigh inter-individual variation and therefore could form the basis for personalised clinical management in the future.
2022-05-03 | GSE178936 | GEO
Project description:Aneuploidy is a hallmark of tumor cells and yet the precise relationship between aneuploidy and a cell’s proliferative ability, or cellular fitness, has remained elusive. In this study we have combined a detailed analysis of aneuploid clones isolated from laboratory-evolved populations of Saccharomyces cerevisiae with a systematic, genome-wide screen for the fitness effects of telomeric amplifications to address the relationship between aneuploidy and cellular fitness. We found that aneuploid clones rise to high population frequencies in nutrient-limited evolution experiments and show increased fitness relative to wild-type. Direct competition experiments confirmed that three out of four aneuploid events isolated from evolved populations were themselves sufficient to improve fitness. To expand the scope beyond this small number of exemplars, we created a genome-wide collection of >1,800 diploid yeast strains each containing a different telomeric amplicon (Tamp) ranging in size from 0.4 to 1,000kb. Using pooled competition experiments in nutrient-limited chemostats followed by high-throughput sequencing of strain-identifying barcodes, we determined the fitness effects of these >1,800 Tamps under three different conditions. Our data revealed that the fitness landscape explored by telomeric amplifications is much broader than that explored by single-gene amplifications. As also observed in the evolved clones, we found the fitness effects of most Tamps to be condition specific with a minority showing common effects in all three conditions. By integrating our data with previous work that examined the fitness effects of single-gene amplifications genome wide, we found that a small number of genes within each Tamp are centrally responsible for each Tamp’s fitness effects. Our genome-wide Tamp screen confirmed that telomeric amplifications identified in laboratory-evolved populations generally increased fitness. Our results show that Tamps are mutations that produce large, typically condition-dependent changes in fitness that are important drivers of increased fitness in asexually evolving populations. Each of these arrays is a Comparative Genomic Hybridization experiment to detect copy number differences between a reference strain and a strain of interest.
2015-04-12 | E-GEOD-67769 | biostudies-arrayexpress
Project description:Pleiotropic effects of trans-regulatory mutations on gene expression and fitness
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