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E-GEOD-60244 - Transcriptional Profiling is Superior to Procalcitonin to Discriminate Bacterial vs. Viral Lower Respiratory Tract Infections in Hospitalized Adults

Status
Released on 14 September 2015, last updated on 20 September 2015
Organism
Homo sapiens
Samples (158)
Array (1)
Protocols (7)
Description
Background: Distinguishing between bacterial and viral lower respiratory tract infections (LRTI) in hospitalized patients remains challenging. Transcriptional profiling is a promising tool for improving diagnosis in LRTI. Methods: We performed whole blood transcriptional analysis in a cohort of 118 adult patients (median [IQR] age, 61 [50-76] years) hospitalized with bacterial, viral or viral-bacterial LRTI, and 40 age-matched healthy controls (60 [46-70] years). We applied class comparisons, modular analysis and class prediction algorithms to identify distinct biosignatures for bacterial and viral LRTI, which were validated in an independent group of patients. Results: Patients were classified as bacterial (B, n=22), viral (V, n=71) and bacterial-viral LRTI (BV, n=25) based on comprehensive microbiologic testing. Compared with healthy controls statistical group comparisons (p<0.01; with multiple test corrections) identified 3,376 differentially expressed genes in patients with B-LRTI; 2,391 in V-LRTI, and 2,628 in BV-LRTI. Independent of etiologic pathogen, patients with LRTI demonstrated overexpression of innate immunity and underexpression of adaptive immunity genes. Patients with B-LRTI showed significant overexpression of inflammation (B>BV>V) and neutrophils (B>BV>V) while those with V-LRTI displayed significantly greater overexpression of interferon genes (V>BV>B). The K-Nearest Neighbors (K-NN) algorithm identified 10 classifier genes that discriminated patients with bacterial vs viral LRTI with 97% [95%CI: 84-100] sensitivity and 92% [77-98] specificity. In comparison, procalcitonin classified bacterial vs viral LRTI with 38% [18-62] sensitivity and 91% [76-98] specificity. Conclusions: Transcriptional profiling can be used as a helpful tool for the diagnosis of adults hospitalized with LRTI. 158 samples, no replicates; bacterial LRTI n=22, viral LRTI n=71, bacterial-viral coinfections n=25, and healthy controls n=40
Experiment type
transcription profiling by array 
Contacts
Nicole Baldwin <geo@ncbi.nlm.nih.gov>, Ann R Falsey, Asuncion Mejias, Edward E Walsh, Eleonora Bunsow, Nicolas M Suarez, Octavio Ramilo
Citation
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-60244.idf.txt
Sample and data relationshipE-GEOD-60244.sdrf.txt
Processed data (1)E-GEOD-60244.processed.1.zip
Additional data (1)E-GEOD-60244.additional.1.zip
Array designA-GEOD-10558.adf.txt
Links