Performance in Omics Analyses of Blood Samples in Long-Term Storage: Opportunities for the Exploitation of Existing Biobanks in Environmental Health Research

Dennie G.A.J. Hebels¹, Panagiotis Georgiadis², Hector C. Keun^3,4, Toby J. Athersuch^3,4, Paolo Vineis³, Roel Vermeulen⁵, Lützen Portengen⁵, Ingvar A. Bergdahl⁶, Göran Hallmans⁷, Domenico Palli⁸, Benedetta Bendinelli⁸, Vittorio Krogh⁹, Rosario Tumino¹⁰, Carlotta Sacerdote^11,12, Salvatore Panico¹³, Jos C.S. Kleinjans¹, Theo M.C.M. de Kok¹, Martyn T. Smith¹⁴, and Soterios A. Kyrtopoulos²

¹Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands; ²National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece; ³Imperial College London, MRC-HPA Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, London, UK; ⁴ Imperial College London, Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, London, UK; ⁵Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands; ⁶Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine and Department of Biobank Research, Umeå University, Umeå, Sweden; ⁷Nutrition Research, Department of Public Health and Clinical Medicine and Department of Biobank Research, Umeå University, Umeå, Sweden; ⁸The Institute for Cancer Research and Prevention, Italy; ⁹Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; ¹⁰Cancer Registry and Histopathology Unit, “Civile-M.P. Arezzo” Hospital, Ragusa, Italy; ¹¹Center for Cancer Prevention (CPO-Piemonte), Turin, Italy; ¹²Unit of Epidemiology and Molecular Genetics, Human Genetics Foundation (HuGeF), Turin, Italy; ¹³Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy; ¹⁴Genes and Environment Laboratory, School of Public Health, University of California, Berkeley, California, USA

Advance Publication

Abstract

Background: The suitability for omic analysis of biosamples collected in previous decades and currently stored in biobanks is not known.

Objectives: We evaluated the influence of handling and storage conditions of blood-derived biosamples on transcriptomic, epigenomic (CpG methylation) and plasma metabolomic (UPLC-ToFMS) and wide-target proteomic profiles.

Methods: Initially we collected fresh blood samples without RNA preservative in heparin, EDTA or citrate and held them at room temperature for up to 24hr prior to fractionation into buffy coat, erythrocytes and plasma and freezing at -80^oC or in liquid nitrogen. We developed methodology for RNA isolation from the buffy coats and conducted omic analyses. Finally, we analysed analogous samples from the EPIC-Italy and Northern Sweden Health and Disease Study biobanks.

Results: Microarray-quality RNA could be isolated from buffy coats (including most biobank samples) frozen within 8hr of blood collection, by thawing in RNA preservative. Different anticoagulants influenced the metabolomic, proteomic and, to a lesser extent, transcriptomic profiles. The latter were most affected by the delay (as little as 2hr) prior to blood fractionation, while storage temperature had minimal impact. Effects on metabolomic and proteomic profiles were noted in samples processed 8hr or more after collection, but none due to storage temperature. None of the variables examined significantly influenced the epigenomic profiles. No systematic influence of time-in-storage was observed in samples stored over a period of 13-17 years.

Conclusions: Most samples currently stored in biobanks are amenable to meaningful omics analysis, provided that they satisfy collection and storage criteria defined in this study.

Citation: Hebels DG, Georgiadis P, Keun HC, Athersuch TJ, Vineis P, Vermeulen R, Portengen L, Bergdahl IA, Hallmans G, Palli D, Bendinelli B, Krogh V, Tumino R, Sacerdote C, Panico S, Kleinjans JC, de Kok TM, Smith MT, Kyrtopoulos SA. Environ Health Perspect (): .doi:10.1289/ehp.1205657

Received: June 22, 2012; Accepted: February 4, 2013; Published: February 5, 2013

Advance Publication

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