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Single-cell RNA-seq variant analysis for exploration of genetic heterogeneity in cancer
KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.ORCID-id: 0000-0003-0492-9960
KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.ORCID-id: 0000-0001-8993-048X
KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.ORCID-id: 0000-0001-6990-1905
2019 (Engelska)Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 9524Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Inter-and intra-tumour heterogeneity is caused by genetic and non-genetic factors, leading to severe clinical implications. High-throughput sequencing technologies provide unprecedented tools to analyse DNA and RNA in single cells and explore both genetic heterogeneity and phenotypic variation between cells in tissues and tumours. Simultaneous analysis of both DNA and RNA in the same cell is, however, still in its infancy. We have thus developed a method to extract and analyse information regarding genetic heterogeneity that affects cellular biology from single-cell RNA-seq data. The method enables both comparisons and clustering of cells based on genetic variation in single nucleotide variants, revealing cellular subpopulations corroborated by gene expression-based methods. Furthermore, the results show that lymph node metastases have lower levels of genetic heterogeneity compared to their original tumours with respect to variants affecting protein function. The analysis also revealed three previously unknown variants common across cancer cells in glioblastoma patients. These results demonstrate the power and versatility of scRNA-seq variant analysis and highlight it as a useful complement to already existing methods, enabling simultaneous investigations of both gene expression and genetic variation.

Ort, förlag, år, upplaga, sidor
NATURE PUBLISHING GROUP , 2019. Vol. 9, artikel-id 9524
Nationell ämneskategori
Medicinsk genetik
Identifikatorer
URN: urn:nbn:se:kth:diva-255413DOI: 10.1038/s41598-019-45934-1ISI: 000473417000015PubMedID: 31267007Scopus ID: 2-s2.0-85069268174OAI: oai:DiVA.org:kth-255413DiVA, id: diva2:1342873
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QC 20190814

Tillgänglig från: 2019-08-14 Skapad: 2019-08-14 Senast uppdaterad: 2019-10-16Bibliografiskt granskad

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Fasterius, ErikUhlén, MathiasAl-Khalili Szigyarto, Cristina

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