Banff 2019 Meeting Report: Molecular diagnostics in solid organ transplantation-Consensus for the Banff Human Organ Transplant (B-HOT) gene panel and open source multicenter validation

Michael Mengel, Alexandre Loupy, Mark Haas, Candice Roufosse, Maarten Naesens, Enver Akalin, Marian C Clahsen-van Groningen, Jessy Dagobert, Anthony J Demetris, Jean-Paul Duong van Huyen, Juliette Gueguen, Fadi Issa, Blaise Robin, Ivy Rosales, Jan H Von der Thüsen, Alberto Sanchez-Fueyo, Rex N Smith, Kathryn Wood, Benjamin Adam, Robert B Colvin, Michael Mengel, Alexandre Loupy, Mark Haas, Candice Roufosse, Maarten Naesens, Enver Akalin, Marian C Clahsen-van Groningen, Jessy Dagobert, Anthony J Demetris, Jean-Paul Duong van Huyen, Juliette Gueguen, Fadi Issa, Blaise Robin, Ivy Rosales, Jan H Von der Thüsen, Alberto Sanchez-Fueyo, Rex N Smith, Kathryn Wood, Benjamin Adam, Robert B Colvin

Abstract

This meeting report from the XV Banff conference describes the creation of a multiorgan transplant gene panel by the Banff Molecular Diagnostics Working Group (MDWG). This Banff Human Organ Transplant (B-HOT) panel is the culmination of previous work by the MDWG to identify a broadly useful gene panel based on whole transcriptome technology. A data-driven process distilled a gene list from peer-reviewed comprehensive microarray studies that discovered and validated their use in kidney, liver, heart, and lung transplant biopsies. These were supplemented by genes that define relevant cellular pathways and cell types plus 12 reference genes used for normalization. The 770 gene B-HOT panel includes the most pertinent genes related to rejection, tolerance, viral infections, and innate and adaptive immune responses. This commercially available panel uses the NanoString platform, which can quantitate transcripts from formalin-fixed paraffin-embedded samples. The B-HOT panel will facilitate multicenter collaborative clinical research using archival samples and permit the development of an open source large database of standardized analyses, thereby expediting clinical validation studies. The MDWG believes that a pathogenesis and pathway based molecular approach will be valuable for investigators and promote therapeutic decision-making and clinical trials.

Keywords: biomarker; biopsy; classification systems: Banff classification; clinical research/practice; diagnostic techniques and imaging; pathology/histopathology.

Conflict of interest statement

The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Michael Mengel received honoraria from Novartis, CSL Behring, Vitaeris. Mark Haas received consulting fees from Shire ViroPharma, AstraZeneca, Novartis, and CareDx, and honoraria from CareDx. Robert Colvin is a consultant for Shire ViroPharma, CSL Behring, Alexion and eGenesis. Candice Roufosse has received consulting fees from Achillion and UCB. Ivy Rosales is a consultant for eGenesis. Enver Akalin received honorarium and research grant support from CareDx. Marian Clahsen‐van Groningen received grant support from Astellas Pharma (paid to the Erasmus MC). A. Jake Demetris receives research support from Q2 Solutions and is a member of an Adjudication Committee for Novartis. None of these conflicts are relevant to this article. The other authors have no conflicts of interest to disclose. None of the authors has a financial interest in NanoString.

© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.

Figures

FIGURE 1
FIGURE 1
Banff Human Organ Transplant (B‐HOT) panel design process and main pathways investigated by this panel. Banff Human Organ Transplant (B‐HOT) panel design process involved 12 transplant expertsfrom 5 universities (Harvard University, Université de Paris, University of Alberta, Imperial College of London, and Erasmus MC Rotterdam). Banff consortium was composed of B. Colvin, R.N. Smith, I. Rosales, M. Mengel, B. Adam, C. Roufosse, M.C. Clahsen‐van Groningen, J.H. von der Thüsen, B. Robin, J. Dagobert, J.‐P. Duong‐van‐Huyen, and A. Loupy. The Banff Human Organ Transplant Panel logo in Figure 1 has been reproduced with permission from NanoString
FIGURE 2
FIGURE 2
Examples of cells, pathways, and genes studied by the B‐HOT panel. Three main pathways can be identified: tissue damage, organ rejection, and immune response. The B‐HOT panel profiles a total of 758 genes across 37 pathways. Green double‐stranded DNA represents gene expression, blue single‐stranded RNA represents RNA expressed by cells or tissue. Cartoons of organs, cells, and other illustrations used in Figure 2 have been retrieved from http://smart.servier.com/, a free medical images bank of Servier
FIGURE 3
FIGURE 3
Data integration platform (DIP) design. Three elements are identified: (1) data production (histology, molecular, and clinical) by participating hospital; (2) DIP (web interface, cloud computing) to centralize, check, and validate all data; and (3) results production by any participating physician/scientist using built in analytical tools

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