Submitted by Haiquan Li (University of Arizona, USA) on May 02 2015
Platform: microarray – [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version]
Pubmed: None listed
Summary Background: Clinical transcriptomics of peripheral blood mononuclear cells (PBMC) are coming into focus as a surrogate approach for prognosis, diagnosis, biomarker discovery and examination disease mechanisms. However, bioassays paired with transcriptomic analytic tools are yet to be developed and made available at point of care. Harnessing personal dynamic genomic responses to tailor patient asthma treatment or prevent disease exacerbations remain unmet medical needs.
Method: We developed a rhinovirus-stimulated peripheral blood based-assay (virogram assay) coupled with single-subject analytics (N-of-1-patwhays) to capture dynamic genome-wide expression and dysregulated pathways to retrospectively predict childhood asthma exacerbation. We hypothesized that some genomic factors might predispose any given individual, healthy or asthmatic, to a set of similar transcriptional responses to rhinovirus stimulation. We first generated a classifier from paired sample microarrays, control and stimulated PBMC from healthy subjects and applied this classifier on the transcriptomic analysis of control and HRV-stimulated PBMC samples (virogram assay) from children with asthma.
Results: The analysis of the different genomic responses of single-subject paired PBMC samples (HRV-stimulated and control) derived from healthy individuals (external dataset) enabled the discovery of dysregulated pathways related to acquired immunity, epigenetics and morphogenesis. The classifier built on these results and applied on the transcriptional analysis derived from the virogram assay predicted that the risk of asthma exacerbation among asthmatic subjects with an accuracy of 70%.
Conclusion: We provide evidence that clinical prognosis can be predicted with a PBMC based-bioassay aligned with adequate single-subject analytics to assess dynamic transcriptomic response to specific disease-associated stimuli.
ID | Title | Cell Type | Timepoint | Reported Virus | Virus Species | Exclusion Reason |
---|---|---|---|---|---|---|
GSM1673558 | M3 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673559 | M3 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673560 | SUB09 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673561 | SUB09 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673562 | SUB12 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673563 | SUB12 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673564 | SUB15 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673565 | SUB15 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673566 | SUB20 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673567 | SUB20 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673568 | SUB22 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673569 | SUB22 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673570 | SUB23 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673571 | SUB23 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673572 | SUB25 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673573 | SUB25 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673574 | SUB29 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673575 | SUB29 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673576 | SUB30 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673577 | SUB30 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673578 | SUBM1 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673579 | SUBM1 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673580 | SUB04 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673581 | SUB04 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673582 | SUB05 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673583 | SUB05 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673584 | SUB10 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673585 | SUB10 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673586 | SUB13 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673587 | SUB13 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673588 | SUB14 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673589 | SUB14 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673590 | SUB16 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673591 | SUB16 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673592 | SUB17 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673593 | SUB17 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673594 | SUB2 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673595 | SUB2 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673596 | SUB21 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673597 | SUB21 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673598 | SUB26 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673599 | SUB26 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673600 | SUB7 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673601 | SUB7 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A | |
GSM1673602 | SUBM2 Patient, Control | peripheral blood mononuclear cell | 24 hrs | control | Uninfected | |
GSM1673603 | SUBM2 Patient, Rhinovirus-exposed | peripheral blood mononuclear cell | 24 hrs | HRV 16 | Rhinovirus A |