Analytical performance of Envisia: a genomic classifier for usual interstitial pneumonia

Abstract

BackgroundClinical guidelines specify that diagnosis of interstitial pulmonary fibrosis (IPF) requires identification of usual interstitial pneumonia (UIP) pattern. While UIP can be identified by high resolution CT of the chest, the results are often inconclusive, making surgical lung biopsy necessary to reach a definitive diagnosis (Raghu et al., Am J Respir Crit Care Med 183(6):788–824, 2011). The Envisia genomic classifier differentiates UIP from non-UIP pathology in transbronchial biopsies (TBB), potentially allowing patients to avoid an invasive procedure (Brown et al., Am J Respir Crit Care Med 195:A6792, 2017). To ensure patient safety and efficacy, a laboratory developed test (LDT) must meet strict regulatory requirements for accuracy, reproducibility and robustness. The analytical characteristics of the Envisia test are assessed and reported here.MethodsThe Envisia test utilizes total RNA extracted from TBB samples to perform Next Generation RNA Sequencing. The gene count data from 190 genes are then input to the Envisia genomic classifier, a machine learning algorithm, to output either a UIP or non-UIP classification result. We characterized the stability of RNA in TBBs during collection and shipment, and evaluated input RNA mass and proportions on the limit of detection of UIP. We evaluated potentially interfering substances such as blood and genomic DNA. Intra-run, inter-run, and inter-laboratory reproducibility of test results were also characterized.ResultsRNA content within TBBs preserved in RNAprotect is stable for up to 14 days with no detectable change in RNA quality. The Envisia test is tolerant to variation in RNA input (5 to 30 ng), with no impact on classifier results. The Envisia test can tolerate dilution of non-UIP and UIP classification signals at the RNA level by up to 60% and 20%, respectively. Analytical specificity studies utilizing UIP and non-UIP samples mixed with genomic DNA (up to 30% relative input) demonstrated no impact to classifier results. The Envisia test tolerates up to 22% of blood contamination, well beyond the level observed in TBBs. The test is reproducible from RNA extraction through to Envisia test result (standard deviation of 0.20 for Envisia classification scores on > 7-unit scale).ConclusionsThe Envisia test demonstrates the robust analytical performance required of an LDT. Envisia can be used to inform the diagnoses of patients with suspected IPF.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-017-0485-4) contains supplementary material, which is available to authorized users.

Impact of Transcriptomics on Our Understanding of Pulmonary Fibrosis

“…This approach was solely based on transcriptional data concordant with UIP pathological findings without integration of clinical information, or comparison to patient-level diagnoses by multidisciplinary teams, the current diagnostic gold standard ( 19 ). The same group continued improving genomic classifiers to differentiate UIP from non-UIP and demonstrate high robustness toward lung tissue collection using transbronchial biopsy ( 81 , 82 ) (Figure 1 ; Table 2 ).…”

Tripartite motif containing 35 contributes to the proliferation, migration, and invasion of lung cancer cellsin vitroandin vivo

“…In recent years, lung cancer has leaped to the highest morbidities and mortality rates among all cancers [1,2]. Among the different subtypes of lung cancer, non-small cell lung cancer (NSCLC) was the major subtype, accounting for approximately 80-85% of cases [3][4][5], with 2.1 million new lung cancer cases and 1.8 million deaths predicted in 2019 [6]. Although the treatment of lung cancer has made great breakthroughs in recent decades, traditional chemotherapeutic drugs lacked specific targeting specificity for NSCLC, or had toxic side effects on patients and limited efficacy [7].…”

Idiopathic Pulmonary Fibrosis: A Case of Mistaken Identity

“…Interstitial lung disease (ILD) is a group of fibrotic lung disorders with an estimated prevalence of 67-81 per 100,000 people [2,3]. ILDs can be categorized into four groups: 1) ILD of known causes (e.g., connective tissue diseases, environmental or occupational exposures along with drug-induced condition; 2) sarcoidosis; 3) idiopathic interstitial pneumonia; 4) lymphangioleiomyomatosis, Langerhans' cell histiocytosis, alveolar lipoproteinosis or eosinophilic pneumonia [3,4]. Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic progressive fibrosis of the lung tissue and defined by the histopathological and or radiographic pattern of UIP [5,6].…”

“…Our patient presented with similar findings as outlined by the American Thoracic Society (ATS). One of the critical findings of ILD is the usual interstitial pneumonia (UIP) pattern seen in the specimen collected via the surgical lung biopsy or by high resolution computed tomography of the chest (HRCT) [4,3]. Envisia Genomic Classifier is a noninvasive diagnostic test that utilizes an RNA sequencing assay to amplify exonic transcriptions obtained from 15 ng of RNA from 3-5 transbronchial lung biopsies (TBB) [3].…”