A drug screen carried out in a zebrafish larval model of spontaneous brain haemorrhage to identify novel treatments for stroke

A drug screen carried out in a zebrafish larval model of spontaneous brain haemorrhage to identify novel treatments for stroke

Proteomics analysis of zebrafish larval head tissue following intracerebral haemorrhage and treatment with ramipril or quinapril

Proteomics analysis of zebrafish larval head tissue following intracerebral haemorrhage and treatment with ramipril or quinapril

Cancers arise through the acquisition of oncogenic mutations and grow by clonal expansion. Here we reveal that most mutagenic DNA lesions are not resolved into a mutated DNA base pair within a single cell cycle. Instead, DNA lesions segregate, unrepaired, into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. We characterize this process in mutagen-induced mouse liver tumours and show that DNA replication across persisting lesions can produce multiple alternative alleles in successive cell divisions, thereby generating both multiallelic and combinatorial genetic diversity. The phasing of lesions enables accurate measurement of strand-biased repair processes, quantification of oncogenic selection and fine mapping of sister-chromatid-exchange events. Finally, we demonstrate that lesion segregation is a unifying property of exogenous mutagens, including UV light and chemotherapy agents in human cells and tumours, which has profound implications for the evolution and adaptation of cancer genomes. The data submitted here is analysis output based on primary data submitted to the EBI under the indicated accession PRJEB37808.

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RADseq Protocol. An explicit description of the RADseq protocol, listing the methodology, reagents and equipment for amplifying and sequencing genomic libraries with an Illumina HiSeq. (XML 63Â kb)

RADseq Protocol. An explicit description of the RADseq protocol, listing the methodology, reagents and equipment for amplifying and sequencing genomic libraries with an Illumina HiSeq. (XML 63Â kb)

Gene annotation data output by blastx as associated with SNPs considered to be most strongly under selection. Tab 1 lists annotations for 49 scaffolds containing SNPs differentiated between lineages A and B. Tab 2 lists annotations for 39 scaffolds containing SNPs differentiated between earthworms found on former mine sites and proximal control sites. (XML 80Â kb)

Lineage B genome locations of all SNPs, including respective values output by Bayescan, PCAdapt and Fisherâ s exact test when comparing populations for signals of selection. (ZIP 479Â kb)