Real_time_ssRNAseq_flow_pilot

Real time ssRNAseq flow pilot

Type: Transcriptome Analysis
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001015452	Abstract: Children with Down syndrome have a 150-fold increased risk of developing myeloid leukaemia (ML-DS). Unusually for a childhood leukaemia, ML-DS arises from a preleukaemic state, termed transient abnormal myelopoiesis (TAM), and via a conserved sequence of mutations. Here, we examined the relationship between the genetic and transcriptional evolution of ML-DS from a rich collection of primary patient samples through single cell mRNA sequencing, complemented by phylogenetic analyses in progressive disease. We distilled the transcriptional consequence of each genetic step in the evolution of ML-DS, showing that TAM-defining GATA1 mutations account for most of the ML-DS transcriptome, including those of progressive disease. This transcriptional backbone may thus represent a common vulnerability in ML-DS. We extracted the transcriptional difference between TAM and ML-DS which, unexpectedly, reflected features shared across childhood leukaemia. Our approach delineates the transcriptional evolution of ML-DS and provides an analytical blueprint for distilling consequences of mutations directly from patient samples.	Illumina HiSeq 4000 Illumina NovaSeq 6000	1
EGAD00001015673	Refractory cancers may arise either through the acquisition of resistance mechanisms or represent distinct disease states. The origin of childhood T-cell acute lymphoblastic leukaemia (T-ALL) that does not respond to initial treatment, i.e. refractory disease, is unknown. Refractory T-ALL carries a poor prognosis and cannot be predicted at diagnosis. Here, we perform single cell mRNA sequencing of T-ALL from 58 children (84 samples) who did, or did not respond to initial treatment. We identify a transcriptionally distinctive blast population, exhibiting features of innate-like lymphocytes, as the major source of refractory disease. Evidence of such blasts at diagnosis heralds refractory disease across independent datasets and is associated with survival in a large, contemporary trial cohort. Our findings portray refractory T-ALL as a distinct disease with the potential for immediate clinical utility. This dataset contains 56 single-cell RNA sequencing data files with corresponding single-cell T cell receptor sequencing data files. The data here form the validation cohort in our paper.	Illumina NovaSeq 6000	1

Publications	Citations
A non-canonical lymphoblast in refractory childhood T-cell leukaemia. Lim BSJ, Whitfield HJ, Trinh MK, Bloye G, Thomas R, Anderson ND, Wenger A, Hodder A, Treger TD, Lee-Six H, Coorens THH, Parks C, Ogbonnah T, Pölönen P, Mullighan CG, Teachey DT, Xu J, Tan K, Hagleitner M, Kester L, van Leeuwen FN, Beattie G, Mansour MR, Williams O, Bartram J, Adams S, Jardine L, Behjati S, O'Connor D. Nat Commun 16: 2025 9397	0

Publications

Citations

A non-canonical lymphoblast in refractory childhood T-cell leukaemia.
Lim BSJ, Whitfield HJ, Trinh MK, Bloye G, Thomas R, Anderson ND, Wenger A, Hodder A, Treger TD, Lee-Six H, Coorens THH, Parks C, Ogbonnah T, Pölönen P, Mullighan CG, Teachey DT, Xu J, Tan K, Hagleitner M, Kester L, van Leeuwen FN, Beattie G, Mansour MR, Williams O, Bartram J, Adams S, Jardine L, Behjati S, O'Connor D. Nat Commun 16: 2025 9397