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Quality control parameters on a large dataset of regionally dissected human control brains for whole genome expression studies

Daniah Trabzuni, Mina Ryten, Robert Walker and 5 more

Journal of Neurochemistry · 2011

doi:10.1111/j.1471-4159.2011.07432.x

Abstract

J. Neurochem. (2011) 119 , 275–282. We are building an open‐access database of regional human brain expression designed to allow the genome‐wide assessment of genetic variability on expression. Array and RNA sequencing technologies make assessment of genome‐wide expression possible. Human brain tissue is a challenging source for this work because it can only be obtained several and variable hours post‐mortem and after varying agonal states. These variables alter RNA integrity in a complex manner. In this report, we assess the effect of post‐mortem delay, agonal state and age on gene expression, and the utility of pH and RNA integrity number as predictors of gene expression as measured on 1266 Affymetrix Exon Arrays. We assessed the accuracy of the array data using QuantiGene, as an independent non‐PCR‐based method. These quality control parameters will allow database users to assess data accuracy. We report that within the parameters of this study post‐mortem delay, agonal state and age have little impact on array quality, array data are robust to variable RNA integrity, and brain pH has only a small effect on array performance. QuantiGene gave very similar expression profiles as array data. This study is the first step in our initiative to make human, regional brain expression freely available.

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References 35

  1. 1.
  2. 2.

    Bahar B, Monahan FJ, Moloney AP, Schmidt O, MacHugh DE, Sweeney T. Long-term stability of RNA in post-mortem bovine skeletal muscle, liver and subcutaneous adipose tissues. BMC Mol. Biol. 2007;8:108.

    Not in our library10.1186/1471-2199-8-108

  3. 3.

    Barrachina M, Castano E, Ferrer I. TaqMan PCR assay in the control of RNA normalization in human post-mortem brain tissue. Neurochem. Int. 2006;49:276-284.

    Not in our library10.1016/j.neuint.2006.01.018

  4. 4.

    Beach TG, Sue LI, Walker DG, Roher AE, Lue L, Vedders L, Connor DJ, Sabbagh MN, Rogers J. The Sun Health Research Institute Brain Donation Program: description and experience, 1987–2007. Cell Tissue Bank. 2008;9:229-245.

    Not in our library10.1007/s10561-008-9067-2

  5. 5.

    Birdsill AC, Walker DG, Lue L, Sue LI, Beach TG. Postmortem interval effect on RNA and gene expression in human brain tissue. Cell Tissue Bank. 2010.

    Not in our library10.1007/s10561-010-9210-8

  6. 6.

    Burke WJ, O’Malley KL, Chung HD, Harmon SK, Miller JP, Berg L. Effect of pre- and postmortem variables on specific mRNA levels in human brain. Brain Res. Mol. Brain Res. 1991;11:37-41.

    Not in our library10.1016/0169-328x(91)90018-s

  7. 7.

    Canales RD, Luo Y, Willey JC, et al. Evaluation of DNA microarray results with quantitative gene expression platforms. Nat. Biotechnol. 2006;24:1115-1122.

    Not in our library10.1038/nbt1236

  8. 8.

    Chervoneva I, Li Y, Schulz S, Croker S, Wilson C, Waldman SA, Hyslop T. Selection of optimal reference genes for normalization in quantitative RT-PCR. BMC Bioinform. 2010;11:253.

    Not in our library10.1186/1471-2105-11-253

  9. 9.

    Chevyreva I, Faull RL, Green CR, Nicholson LF. Assessing RNA quality in postmortem human brain tissue. Exp. Mol. Pathol. 2008;84:71-77.

    Not in our library10.1016/j.yexmp.2007.08.019

  10. 10.

    Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 1987;162:156-159.

    Not in our library10.1006/abio.1987.9999

  11. 11.

    Coulson DT, Brockbank S, Quinn JG, Murphy S, Ravid R, Irvine GB, Johnston JA. Identification of valid reference genes for the normalization of RT qPCR gene expression data in human brain tissue. BMC Mol. Biol. 2008;9:46.

    Not in our library10.1186/1471-2199-9-46

  12. 12.

    Durrenberger PF, Fernando S, Kashefi SN, et al. Effects of antemortem and postmortem variables on human brain mRNA quality: a BrainNet Europe study. J. Neuropathol. Exp. Neurol. 2010;69:70-81.

    Not in our library10.1097/nen.0b013e3181c7e32f

  13. 13.

    Gilbert JM, Brown BA, Strocchi P, Bird ED, Marotta CA. The preparation of biologically active messenger RNA from human postmortem brain tissue. J. Neurochem. 1981;36:976-984.

    Not in our library10.1111/j.1471-4159.1981.tb01689.x

  14. 14.

    Glanzer JG, Haydon PG, Eberwine JH. Expression profile analysis of neurodegenerative disease: advances in specificity and resolution. Neurochem. Res. 2004;29:1161-1168.

    Not in our library10.1023/b:nere.0000023603.17615.8c

  15. 15.

    Glasel JA. Validity of nucleic acid purities monitored by 260nm/280nm absorbance ratios. BioTechniques. 1995;18:62-63.

    Not in our library

  16. 16.

    Hall JS, Leong HS, Armenoult LS, et al. Exon-array profiling unlocks clinically and biologically relevant gene signatures from formalin-fixed paraffin-embedded tumour samples. Br. J. Cancer. 2011;104:971-981.

    Not in our library10.1038/bjc.2011.66

  17. 17.

    Hardy JA, Wester P, Winblad B, Gezelius C, Bring G, Eriksson A. The patients dying after long terminal phase have acidotic brains; implications for biochemical measurements on autopsy tissue. J. Neural Transm. 1985;61:253-264.

    Not in our library10.1007/bf01251916

  18. 18.

    Hardy J, Trabzuni D, Ryten M. Whole genome expression as a quantitative trait. Biochem. Soc. Trans. 2009;37:1276-1277.

    Not in our library10.1042/bst0371276

  19. 19.

    Harrison PJ, Heath PR, Eastwood SL, Burnet PW, McDonald B, Pearson RC. The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: selective mRNA vulnerability and comparison with their encoded proteins. Neurosci. Lett. 1995;200:151-154.

    Not in our library10.1016/0304-3940(95)12102-a

  20. 20.

    Imbeaud S, Graudens E, Boulanger V, Barlet X, Zaborski P, Eveno E, Mueller O, Schroeder A, Auffray C. Towards standardization of RNA quality assessment using user-independent classifiers of microcapillary electrophoresis traces. Nucleic Acids Res. 2005;33:e56.

    Not in our library10.1093/nar/gni054

  21. 21.
  22. 22.

    Li JZ, Meng F, Tsavaler L, et al. Sample matching by inferred agonal stress in gene expression analyses of the brain. BMC Genomics. 2007;8:336.

    Not in our library10.1186/1471-2164-8-336

  23. 23.

    Lockstone HE. Exon array data analysis using Affymetrix power tools and R statistical software. Brief Bioinform. 2011.

    Not in our library10.1093/bib/bbq086

  24. 24.

    Mexal S, Berger R, Adams CE, Ross RG, Freedman R, Leonard S. Brain pH has a significant impact on human postmortem hippocampal gene expression profiles. Brain Res. 2006;1106:1-11.

    Not in our library10.1016/j.brainres.2006.05.043

  25. 25.

    Millar T, Walker R, Arango JC, Ironside JW, Harrison DJ, MacIntyre DJ, Blackwood D, Smith C, Bell JE. Tissue and organ donation for research in forensic pathology: the MRC Sudden Death Brain and Tissue Bank. J. Pathol. 2007;213:369-375.

    Not in our library10.1002/path.2247

  26. 26.

    Monoranu CM, Apfelbacher M, Grunblatt E, et al. pH measurement as quality control on human post mortem brain tissue: a study of the BrainNet Europe consortium. Neuropathol. Appl. Neurobiol. 2009;35:329-337.

    Not in our library10.1111/j.1365-2990.2008.01003a.x

  27. 27.

    Myers AJ, Gibbs JR, Webster JA, et al. A survey of genetic human cortical gene expression. Nat. Genet. 2007;39:1494-1499.

    Not in our library10.1038/ng.2007.16

  28. 28.

    Ross J. mRNA stability in mammalian cells. Microbiol. Rev. 1995;59:423-450.

    Not in our library10.1128/mr.59.3.423-450.1995

  29. 29.

    Sajdel-Sulkowska EM, Majocha RE, Salim M, Zain SB, Marotta CA. The postmortem Alzheimer brain is a source of structurally and functionally intact astrocytic messenger RNA. J. Neurosci. Methods. 1988;23:173-179.

    Not in our library10.1016/0165-0270(88)90189-6

  30. 30.
  31. 31.

    Sherwood KR, Head MW, Walker R, Smith C, Ironside JW, Fazakerley JK. RNA integrity in post-mortem human vCJD and control brain tissue. Neuropathol. Appl. Neurobiol. 2011;37:633-642.

    Not in our library10.1111/j.1365-2990.2011.01162.x

  32. 32.

    Stan AD, Ghose S, Gao XM, Roberts RC, Lewis-Amezcua K, Hatanpaa KJ, Tamminga CA. Human postmortem tissue: what quality markers matter? Brain Res. 2006;1123:1-11.

    Not in our library10.1016/j.brainres.2006.09.025

  33. 33.

    Tomita H, Vawter MP, Walsh DM, et al. Effect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain. Biol. Psychiatry. 2004;55:346-352.

    Not in our library10.1016/j.biopsych.2003.10.013

  34. 34.

    Vennemann M, Koppelkamm A. mRNA profiling in forensic genetics I: possibilities and limitations. Forensic Sci. Int. 2010;203:71-75.

    Not in our library10.1016/j.forsciint.2010.07.006

  35. 35.

    Weis S, Llenos IC, Dulay JR, Elashoff M, Martinez-Murillo F, Miller CL. Quality control for microarray analysis of human brain samples: The impact of postmortem factors, RNA characteristics, and histopathology. J. Neurosci. Methods. 2007;165:198-209.

    Not in our library10.1016/j.jneumeth.2007.06.001

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