Tan, Joanna Hui Juan, Li Kong, Say, Tai, Joyce A., Poh, Huay Mei, Yao, Fei, Sia, Yee Yen, Lim, Edwin Kok Hao, Takano, Angela Maria, Tan, Daniel Shao-Weng, Javed, Asif ORCID: 0000-0002-6945-9624 and Hillmer, Axel M. (2021). Experimental and bioinformatics considerations in cancer application of single cell genomics. Comp. Struct. Biotechnol. J.., 19. S. 343 - 355. AMSTERDAM: ELSEVIER. ISSN 2001-0370

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Abstract

Single cell genomics offers an unprecedented resolution to interrogate genetic heterogeneity in a patient's tumour at the intercellular level. However, the DNA yield per cell is insufficient for today's sequencing library preparation protocols. This necessitates DNA amplification which is a key source of experimental noise. We provide an evaluation of two protocols using micro-fluidics based amplification for whole exome sequencing, which is an experimental scenario commonly used in single cell genomics. The results highlight their respective biases and relative strengths in identification of single nucleotide variations. Towards this end, we introduce a workflow SoVaTSiC, which allows for quality evaluation and somatic variant identification of single cell data. As proof of concept, the framework was applied to study a lung adenocarcinoma tumour. The analysis provides insights into tumour phylogeny by identifying key mutational events in lung adenocarcinoma evolution. The consequence of this inference is supported by the histology of the tumour and demonstrates usefulness of the approach. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tan, Joanna Hui JuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li Kong, SayUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tai, Joyce A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poh, Huay MeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yao, FeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sia, Yee YenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lim, Edwin Kok HaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Takano, Angela MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tan, Daniel Shao-WengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Javed, AsifUNSPECIFIEDorcid.org/0000-0002-6945-9624UNSPECIFIED
Hillmer, Axel M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-591423
DOI: 10.1016/j.csbj.2020.12.021
Journal or Publication Title: Comp. Struct. Biotechnol. J..
Volume: 19
Page Range: S. 343 - 355
Date: 2021
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 2001-0370
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LUNG-CANCER; INTRATUMOR HETEROGENEITY; GENE-EXPRESSION; POINT MUTATIONS; ASPM; EVOLUTION; VARIANTS; BLADDERMultiple languages
Biochemistry & Molecular Biology; Biotechnology & Applied MicrobiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59142

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