A Robust Method for Estimating Gene Expression States Using Affymetrix Microarray Probe Level Data

Overview

Journal BMC Bioinformatics

Publisher Biomed Central

Specialty Biology

Date 2010 Apr 13

PMID 20380745

Citations 24

Authors

Megu Ohtaki

Keiko Otani

Keiko Hiyama

Naomi Kamei

Kenichi Satoh

Eiso Hiyama

Affiliations

Soon will be listed here.

Abstract

Background: Microarray technology is a high-throughput method for measuring the expression levels of thousand of genes simultaneously. The observed intensities combine a non-specific binding, which is a major disadvantage with microarray data. The Affymetrix GeneChip assigned a mismatch (MM) probe with the intention of measuring non-specific binding, but various opinions exist regarding usefulness of MM measures. It should be noted that not all observed intensities are associated with expressed genes and many of those are associated with unexpressed genes, of which measured values express mere noise due to non-specific binding, cross-hybridization, or stray signals. The implicit assumption that all genes are expressed leads to poor performance of microarray data analyses. We assume two functional states of a gene - expressed or unexpressed - and propose a robust method to estimate gene expression states using an order relationship between PM and MM measures.

Results: An indicator 'probability of a gene being expressed' was obtained using the number of probe pairs within a probe set where the PM measure exceeds the MM measure. We examined the validity of the proposed indicator using Human Genome U95 data sets provided by Affymetrix. The usefulness of 'probability of a gene being expressed' is illustrated through an exploration of candidate genes involved in neuroblastoma prognosis. We identified the candidate genes for which expression states differed (un-expressed or expressed) when compared between two outcomes. The validity of this result was subsequently confirmed by quantitative RT-PCR.

Conclusion: The proposed qualitative evaluation, 'probability of a gene being expressed', is a useful indicator for improving microarray data analysis. It is useful to reduce the number of false discoveries. Expression states - expressed or unexpressed - correspond to the most fundamental gene function 'On' and 'Off', which can lead to biologically meaningful results.

Citing Articles

A multispectral 3D live organoid imaging platform to screen probes for fluorescence guided surgery.

Jeremiasse B, van Ineveld R, Bok V, Kleinnijenhuis M, de Blank S, Alieva M EMBO Mol Med. 2024; 16(7):1495-1514.

PMID: 38831131 PMC: 11251264. DOI: 10.1038/s44321-024-00084-4.

Signature literature review reveals AHCY, DPYSL3, and NME1 as the most recurrent prognostic genes for neuroblastoma.

Chicco D, Sanavia T, Jurman G BioData Min. 2023; 16(1):7.

PMID: 36870971 PMC: 9985261. DOI: 10.1186/s13040-023-00325-1.

Identification of a novel gene signature for neuroblastoma differentiation using a Boolean implication network.

Zage P, Huo Y, Subramonian D, Le Clorennec C, Ghosh P, Sahoo D Genes Chromosomes Cancer. 2023; 62(6):313-331.

PMID: 36680522 PMC: 10257350. DOI: 10.1002/gcc.23124.

Inhibiting Lysine Demethylase 1A Improves L1CAM-Specific CAR T Cell Therapy by Unleashing Antigen-Independent Killing via the FAS-FASL Axis.

Sulejmani O, Grunewald L, Andersch L, Schwiebert S, Klaus A, Winkler A Cancers (Basel). 2021; 13(21).

PMID: 34771652 PMC: 8583435. DOI: 10.3390/cancers13215489.

BTK Inhibition Reverses MDSC-Mediated Immunosuppression and Enhances Response to Anti-PDL1 Therapy in Neuroblastoma.

Ishfaq M, Pham T, Beaman C, Tamayo P, Yu A, Joshi S Cancers (Basel). 2021; 13(4).

PMID: 33669187 PMC: 7919651. DOI: 10.3390/cancers13040817.

References

Calza S, Raffelsberger W, Ploner A, Sahel J, Leveillard T, Pawitan Y . Filtering genes to improve sensitivity in oligonucleotide microarray data analysis. Nucleic Acids Res. 2007; 35(16):e102. PMC: 2018638. DOI: 10.1093/nar/gkm537. View

Jongeneel C, Iseli C, Stevenson B, Riggins G, Lal A, Mackay A . Comprehensive sampling of gene expression in human cell lines with massively parallel signature sequencing. Proc Natl Acad Sci U S A. 2003; 100(8):4702-5. PMC: 153619. DOI: 10.1073/pnas.0831040100. View

Alaminos M, Mora J, Cheung N, Smith A, Qin J, Chen L . Genome-wide analysis of gene expression associated with MYCN in human neuroblastoma. Cancer Res. 2003; 63(15):4538-46. View

Hiyama E, Iehara T, Sugimoto T, Fukuzawa M, Hayashi Y, Sasaki F . Effectiveness of screening for neuroblastoma at 6 months of age: a retrospective population-based cohort study. Lancet. 2008; 371(9619):1173-80. DOI: 10.1016/S0140-6736(08)60523-1. View

Li C, Hung Wong W . Model-based analysis of oligonucleotide arrays: model validation, design issues and standard error application. Genome Biol. 2001; 2(8):RESEARCH0032. PMC: 55329. DOI: 10.1186/gb-2001-2-8-research0032. View

Li C, Wong W . Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. Proc Natl Acad Sci U S A. 2001; 98(1):31-6. PMC: 14539. DOI: 10.1073/pnas.98.1.31. View

Hiyama K, Otani K, Ohtaki M, Satoh K, Kumazaki T, Takahashi T . Differentially expressed genes throughout the cellular immortalization processes are quite different between normal human fibroblasts and endothelial cells. Int J Oncol. 2005; 27(1):87-95. View

Lastowska M, Viprey V, Santibanez-Koref M, Wappler I, Peters H, Cullinane C . Identification of candidate genes involved in neuroblastoma progression by combining genomic and expression microarrays with survival data. Oncogene. 2007; 26(53):7432-44. DOI: 10.1038/sj.onc.1210552. View

Martinez T, Pascual A . Gene expression profile in beta-amyloid-treated SH-SY5Y neuroblastoma cells. Brain Res Bull. 2007; 72(4-6):225-31. DOI: 10.1016/j.brainresbull.2007.01.010. View

10.

Irizarry R, Hobbs B, Collin F, Beazer-Barclay Y, Antonellis K, Scherf U . Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003; 4(2):249-64. DOI: 10.1093/biostatistics/4.2.249. View

11.

Zilliox M, Irizarry R . A gene expression bar code for microarray data. Nat Methods. 2007; 4(11):911-3. PMC: 3154617. DOI: 10.1038/nmeth1102. View

12.

Millenaar F, Okyere J, May S, van Zanten M, Voesenek L, Peeters A . How to decide? Different methods of calculating gene expression from short oligonucleotide array data will give different results. BMC Bioinformatics. 2006; 7:137. PMC: 1431565. DOI: 10.1186/1471-2105-7-137. View

13.

Irizarry R, Bolstad B, Collin F, Cope L, Hobbs B, Speed T . Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res. 2003; 31(4):e15. PMC: 150247. DOI: 10.1093/nar/gng015. View

14.

McClintick J, Edenberg H . Effects of filtering by Present call on analysis of microarray experiments. BMC Bioinformatics. 2006; 7:49. PMC: 1409797. DOI: 10.1186/1471-2105-7-49. View

15.

Wu C, Carta R, Zhang L . Sequence dependence of cross-hybridization on short oligo microarrays. Nucleic Acids Res. 2005; 33(9):e84. PMC: 1140085. DOI: 10.1093/nar/gni082. View

16.

Sah N, Khan Z, Khan G, Bisen P . Structural, functional and therapeutic biology of survivin. Cancer Lett. 2006; 244(2):164-71. DOI: 10.1016/j.canlet.2006.03.007. View

17.

Seeger R, Brodeur G, Sather H, Dalton A, Siegel S, Wong K . Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med. 1985; 313(18):1111-6. DOI: 10.1056/NEJM198510313131802. View

18.

Kaneko M, Tsuchida Y, Uchino J, Takeda T, IWAFUCHI M, Ohnuma N . Treatment results of advanced neuroblastoma with the first Japanese study group protocol. Study Group of Japan for Treatment of Advanced Neuroblastoma. J Pediatr Hematol Oncol. 1999; 21(3):190-7. DOI: 10.1097/00043426-199905000-00006. View

19.

Hubbell E, Liu W, Mei R . Robust estimators for expression analysis. Bioinformatics. 2002; 18(12):1585-92. DOI: 10.1093/bioinformatics/18.12.1585. View

20.

Komatsu M, Hiyama K, Tanimoto K, Yunokawa M, Otani K, Ohtaki M . Prediction of individual response to platinum/paclitaxel combination using novel marker genes in ovarian cancers. Mol Cancer Ther. 2006; 5(3):767-75. DOI: 10.1158/1535-7163.MCT-05-0408. View