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The use of haplotype-specific transcripts improves sample annotation consistency

Hartmann, Nicole and Luesink, Evert and Khokhlovich, Edward and Szustakowski, Joseph and Baeriswyl, Lukas and Peterson, Joshua and Scherer, Andreas and Nirmala, Nanguneri and Staedtler, Frank (2014) The use of haplotype-specific transcripts improves sample annotation consistency. Biomarker Research, 2 (17).

Abstract

Background: Exact sample annotation in expression microarray datasets is essential for any type of pharmacogenomics research.
Materials and methods: Candidate markers were explored through the application of Hartigans’ dip test statistics to a publically available human whole genome microarray dataset. The marker performance was tested on 188 serial samples from 53 donors and of variable tissue origin from five public microarray datasets.
Results: A qualified transcript marker panel consisting of three probe sets for human leukocyte antigens HLA-DQA1 (2 probe sets) and HLA-DRB4 identified sample donor identifier inconsistencies in about 5% of the test samples. About 3% of the test samples require root-cause analysis due to unresolvable inaccuracies.
Conclusions: The transcript marker panel consisting of HLA-DQA1 and HLA-DRB4 represents a robust, tissue-independent composite marker to assist control donor annotation concordance at the transcript level. Allele-selectivity of HLA genes renders them good candidates for “fingerprinting” with donor specific expression pattern.

Item Type: Article
Keywords: HLA-DQA1, HLA-DRB4, microarray quality control (QC), biomarkers, dip test, mRNA
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/23306

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