An integrated molecular diagnostic report for heart transplant biopsies using an ensemble of diagnostic algorithms
Section snippets
Population
This prospective study was approved by the ethics review board of each center (see Table S1 online) and is registered at ClinicalTrials.gov (NCT02670408). As described elsewhere,12 biopsies were collected prospectively for clinical indications or by protocol, and then processed for histology and human leukocyte antibody (HLA) testing as per local standard of care. Histology interpretation followed ISHLT guidelines.3, 22
Microarray analysis
As detailed elsewhere,12 purified total RNA from 889 EMBs, which included
Biopsy population
Clinically indicated, protocol, and follow-up EMBs from 454 patients were collected in 2 cohorts: cohort 331 (N = 331) from the earlier study12 and a new cohort of 558 biopsies (Table 1, and Table S2 online). Cardiomyopathy and coronary artery disease were the common primary diseases.
Histology grades and molecular scores were translated to a common nomenclature13 (see Methods): TCMR, pTCMR, ABMR, and pABMR. Frequencies of the histologic classes in Cohorts 331 and 558 are presented in Table 2
Discussion
Having found value in molecular EMB assessment (especially after incorporating injury estimates),13 in the present study we aimed to develop an ensemble of estimates into a biopsy report and examine automated sign-out. We established that machine-learning algorithms trained in one cohort perform similarly in future biopsies despite differences in case mix. We showed that Model 2 incorporating injury demonstrated similar relationships to histologic rejection as Model 1 and correlated with DSA
Disclosure statement
P.F.H. holds shares in Transcriptome Sciences, Inc., a University of Alberta research company with an interest in molecular diagnostics, and has been a symposium speaker for One Lambda. The other authors no conflicts of interest to disclose.
This study was supported by funds and/or resources from Genome Canada, the Canada Foundation for Innovation, the University of Alberta Hospital Foundation, the Alberta Ministry of Advanced Education and Technology, the Mendez National Institute of
Supplementary data
Supplementary data associated with this article can be found in the online version at www.jhltonline.org/.
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