Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
J Am Med Inform Assoc. 2012 Nov-Dec;19(6):1103-9. doi: 10.1136/amiajnl-2012-000867. Epub 2012 Jun 14.

Transcriptional network predicts viral set point during acute HIV-1 infection.

Author information

  • 1Children's Hospital Informatics Program, Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts, USA. hsun-hsien.chang@childrens.harvard.edu

Abstract

BACKGROUND:

HIV-1-infected individuals with higher viral set points progress to AIDS more rapidly than those with lower set points. Predicting viral set point early following infection can contribute to our understanding of early control of HIV-1 replication, to predicting long-term clinical outcomes, and to the choice of optimal therapeutic regimens.

METHODS:

In a longitudinal study of 10 untreated HIV-1-infected patients, we used gene expression profiling of peripheral blood mononuclear cells to identify transcriptional networks for viral set point prediction. At each sampling time, a statistical analysis inferred the optimal transcriptional network that best predicted viral set point. We then assessed the accuracy of this transcriptional model by predicting viral set point in an independent cohort of 10 untreated HIV-1-infected patients from Malawi.

RESULTS:

The gene network inferred at time of enrollment predicted viral set point 24 weeks later in the independent Malawian cohort with an accuracy of 87.5%. As expected, the predictive accuracy of the networks inferred at later time points was even greater, exceeding 90% after week 4. The composition of the inferred networks was largely conserved between time points. The 12 genes comprising this dynamic signature of viral set point implicated the involvement of two major canonical pathways: interferon signaling (p<0.0003) and membrane fraction (p<0.02). A silico knockout study showed that HLA-DRB1 and C4BPA may contribute to restricting HIV-1 replication.

CONCLUSIONS:

Longitudinal gene expression profiling of peripheral blood mononuclear cells from patients with acute HIV-1 infection can be used to create transcriptional network models to early predict viral set point with a high degree of accuracy.

PMID:
22700869
[PubMed - indexed for MEDLINE]
PMCID:
PMC3534464
Free PMC Article

Images from this publication.See all images (3)Free text

Figure 1
Figure 2
Figure 3
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk