ArticleBMC bioinformatics2002
Sources of variability and effect of experimental approach on expression profiling data interpretation.
Article in BMC bioinformatics, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 180 citations in OpenAlex.
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- Controlling technical variation amongst 6693 patient microarrays of the randomized MINDACT trial.Communications biology · 2020Article
- An embedded method for gene identification problems involving unwanted data heterogeneity.Human genomics · 2019Article
- Conserved transcriptomic profile between mouse and human colitis allows unsupervised patient stratification.Nature communications · 2019Article
- Complex Sources of Variation in Tissue Expression Data: Analysis of the GTEx Lung Transcriptome.American journal of human genetics · 2016Article
- Evidence for genetic regulation of mRNA expression of the dosage-sensitive gene retinoic acid induced-1 (RAI1) in human brain.Scientific reports · 2016Article
- Circulating Biomarkers for Duchenne Muscular Dystrophy.Journal of neuromuscular diseases · 2015Article
- Asynchronous remodeling is a driver of failed regeneration in Duchenne muscular dystrophy.The Journal of cell biology · 2014Article
- Lineage of origin in rhabdomyosarcoma informs pharmacological response.Genes & development · 2014Article
- Intra-platform comparison of 25-mer and 60-mer oligonucleotide Nimblegen DNA microarrays.BMC research notes · 2013Article
- Unlocking the potential of publicly available microarray data using inSilicoDb and inSilicoMerging R/Bioconductor packages.BMC bioinformatics · 2012Article
- C3KO mouse expression analysis: downregulation of the muscular dystrophy Ky protein and alterations in muscle aging.Neurogenetics · 2012Article
- Effects of tissue handling on RNA integrity and microarray measurements from resected breast cancers.Journal of the National Cancer Institute · 2011Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundWe provide a systematic study of the sources of variability in expression profiling data using 56 RNAs isolated from human muscle biopsies (34 Affymetrix MuscleChip arrays), and 36 murine cell culture and tissue RNAs (42 Affymetrix U74Av2 arrays).
resultsWe studied muscle biopsies from 28 human subjects as well as murine myogenic cell cultures, muscle, and spleens. Human MuscleChip arrays (4,601 probe sets) and murine U74Av2 Affymetrix microarrays were used for expression profiling. RNAs were profiled both singly, and as mixed groups. Variables studied included tissue heterogeneity, cRNA probe production, patient diagnosis, and GeneChip hybridizations. We found that the greatest source of variability was often different regions of the same patient muscle biopsy, reflecting variation in cell type content even in a relatively homogeneous tissue such as muscle. Inter-patient variation was also very high (SNP noise). Experimental variation (RNA, cDNA, cRNA, or GeneChip) was minor. Pre-profile mixing of patient cRNA samples effectively normalized both intra- and inter-patient sources of variation, while retaining a high degree of specificity of the individual profiles (86% of statistically significant differences detected by absolute analysis; and 85% by a 4-pairwise comparison survival method).
conclusionsUsing unsupervised cluster analysis and correlation coefficients of 92 RNA samples on 76 oligonucleotide microarrays, we found that experimental error was not a significant source of unwanted variability in expression profiling experiments. Major sources of variability were from use of small tissue biopsies, particularly in humans where there is substantial inter-patient variability (SNP noise).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.