Ena-DATASET-WIMM-01-07-2019-10:59:14:753-341 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001005118 | EGA |
REPOSITORIES: EGA
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Project description:How to design experiments that accelerate knowledge discovery on complex biological landscapes remains a tantalizing question. Here, we present OPEX, an optimal experimental design method to identify informative omics experiments for both experimental space exploration and model training. OPEX-guided exploration of Escherichia coli's cross-behavior potential, when exposed to novel biocide and antibiotic combinations, led to accelerated knowledge discovery with predictive models that are more accurate while needing 44% fewer data to train. Selecting experiments favoring broader exploration followed by fine-tuning emerged as the optimal strategy. This led to the discovery of 29 cross-protection and 4 cross-vulnerability conditions, with further validation revealing the central role of chaperones, stress response proteins and transport pumps in cross-stress exposure. This work demonstrates how active learning can be used to automate omics data collection for training accurate predictive models, evidence-driven decision making and accelerated knowledge discovery in life sciences.
2020-07-09 | GSE144604 | GEO
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Project description:Current approaches to track stem cell clones through differentiation require genetic engineering or rely on sparse somatic DNA variants. Here, we show that targeted single-cell measurements of DNA methylation at single-CpG resolution deliver joint information about cellular differentiation state and clonal identities. We develop EPI-clone, a method for transgene-free lineage tracing based on microfluidic, targeted single-cell DNA methylation analysis. Applied to mouse and human hematopoiesis, we captured hundreds of clonal differentiation trajectories across tens of individuals and almost 400,000 single-cells. Using ground-truth genetic barcodes, we demonstrate that EPI-clone accurately identifies clonal lineages throughout hematopoietic differentiation while at the same time providing cell state resolution similar to transcriptomic data. Applied to unperturbed hematopoiesis in murine ageing, we demonstrate that myeloid bias and low output of old HSCs are restricted to a small number of expanded developmental clones, while many functionally young-like clones persist in old age. In human ageing, we demonstrate that clones carrying CHIP mutations are part of a spectrum of age-related expansions of low-output clones. EPI-clone is compatible with the multiplexed readout of surface protein, somatic variants and RNA from the same single cell. Taken together, EPI-clone enables accurate and transgene-free single-cell lineage tracing on hematopoietic cell state landscapes at scale.
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Project description:Accurate runs of homozygosity estimation from low coverage genome sequences in non-model species
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Project description:2-3 month old female C57Bl/6J mice were intravenously infected with 2x10^6 focus forming units of lymphocytic choriomeningitis virus strain Clone-13. Whole liver tissue was harvested in duplicated from uninfected control mice, uninfected 123d old mice, and from infected at 2, 8, 30, 60, and 123 days post infection. Three TMT 6-plex runs were carried out to monitor the changes in liver protein abundance during the entire course of infection. The first run included samples from day 2 and day 8 after infection along with the uninfected controls. Similarly, the second run included uninfected controls and samples from day 30 and day 60 after infection. The third run included samples day 123 after infection, the corresponding age matched control that was left uninfected for 123 days and the uninfected controls used in the other two runs. The uninfected controls were included in all the three runs as an internal control to monitor reproducibility between the runs.
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Project description:Metagenome derived RubisCO active fosmid clone pcc1FOS81G7
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