Transcriptional Categorization of the Etiology of Pneumonia Syndrome in Pediatric Patients in Malaria-Endemic Areas.
Pediatric acute respiratory distress in tropical settings is very common. Bacterial pneumonia is a major contributor to morbidity and mortality rates and requires adequate diagnosis for correct treatment. A rapid test that could identify bacterial (vs other) infections would have great clinical utility.



We performed RNA (RNA-seq) sequencing and analyzed the transcriptomes of 68 pediatric patients with well-characterized clinical phenotype to identify transcriptional features associated with each disease class. We refined the features to predictive models (support vector machine, elastic net) and validated those models in an independent test set of 37 patients (80%-85% accuracy).



We have identified sets of genes that are differentially expressed in pediatric patients with pneumonia syndrome attributable to different infections and requiring different therapeutic interventions. Findings of this study demonstrate that human transcription signatures in infected patients recapitulate the underlying biology and provide models for predicting a bacterial diagnosis to inform treatment.
Broad Institute of MIT and Harvard, Cambridge.
Jacob
J
Silterra
Broad Institute of MIT and Harvard, Cambridge.|Massachusetts General Hospital.|Harvard Medical School.
Michael A
MA
Gillette
Barcelona Institute for Global Health, Barcelona Centre of International Health Research, Hospital Clínic-Universitat de Barcelona.|Centro de Investigação em Saúde de Manhiça.
Miguel
M
Lanaspa
Broad Institute of MIT and Harvard, Cambridge.|Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health.
Karell G
KG
Pellé
Broad Institute of MIT and Harvard, Cambridge.|Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health.
Clarissa
C
Valim
Broad Institute of MIT and Harvard, Cambridge.
Rushdy
R
Ahmad
Centro de Investigação em Saúde de Manhiça.|National Institute of Health, Health Ministry, Maputo, Mozambique.
Sozinho
S
Acácio
Broad Institute of MIT and Harvard, Cambridge.
Katherine D
KD
Almendinger
Broad Institute of MIT and Harvard, Cambridge.|Bioinformatics Program, Boston University.
Yan
Y
Tan
Barcelona Institute for Global Health, Barcelona Centre of International Health Research, Hospital Clínic-Universitat de Barcelona.|Centro de Investigação em Saúde de Manhiça.
Lola
L
Madrid
Barcelona Institute for Global Health, Barcelona Centre of International Health Research, Hospital Clínic-Universitat de Barcelona.|Centro de Investigação em Saúde de Manhiça.
Pedro L
PL
Alonso
Broad Institute of MIT and Harvard, Cambridge.
Steven A
SA
Carr
Broad Institute of MIT and Harvard, Cambridge.
Roger C
RC
Wiegand
Barcelona Institute for Global Health, Barcelona Centre of International Health Research, Hospital Clínic-Universitat de Barcelona.|Institució Catalana de Recerca i Estudis Avançats, Passeig Lluís Companys 23, 08010 Barcelona.|Centro de Investigação em Saúde de Manhiça.
Quique
Q
Bassat
Broad Institute of MIT and Harvard, Cambridge.|Department of Medicine, University of California, San Diego.
Jill P
JP
Mesirov
Broad Institute of MIT and Harvard, Cambridge.|Harvard Medical School.|Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health.|Brigham and Women's Hospital, Boston, Massachusetts.
Danny A
DA
Milner
Broad Institute of MIT and Harvard, Cambridge.|Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health.
Dyann F
DF
Wirth
D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D057089:Pathology, Molecular / Q000379:methods*; D011014:Pneumonia / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology*; D017423:Sequence Analysis, RNA
Pneumonia; RNA-Seq; biomarkers; gene expression; machine learning