Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

<jats:p>Network analysis of transcriptional signature typically relies on direct interaction between two highly expressed genes. However, this approach misses indirect and biological relevant interactions through a third factor (hub). Here we determine whether a hub-based network analysis can select an improved signature subset that correlates with a biological change in a stronger manner than the original signature. We have previously reported an interferon-related transcriptional signature (THP1r2<jats:italic>Mtb</jats:italic>-induced) from<jats:italic>Mycobacterium tuberculosis</jats:italic>(<jats:italic>M. tb</jats:italic>)-infected THP-1 human macrophage. We selected hub-connected THP1r2<jats:italic>Mtb</jats:italic>-induced genes into the refined network signature T<jats:italic>Mtb</jats:italic>-iNet and grouped the excluded genes into the excluded signature T<jats:italic>Mtb</jats:italic>-iEx. T<jats:italic>Mtb</jats:italic>-iNet retained the enrichment of binding sites of interferon-related transcription factors and contained relatively more interferon-related interacting genes when compared to THP1r2<jats:italic>Mtb</jats:italic>-induced signature. T<jats:italic>Mtb</jats:italic>-iNet correlated as strongly as THP1r2<jats:italic>Mtb</jats:italic>-induced signature on a public transcriptional dataset of patients with pulmonary tuberculosis (PTB). T<jats:italic>Mtb</jats:italic>-iNet correlated more strongly in CD4<jats:sup>+</jats:sup>and CD8<jats:sup>+</jats:sup>T cells from PTB patients than THP1r2<jats:italic>Mtb</jats:italic>-induced signature and T<jats:italic>Mtb</jats:italic>-iEx. When T<jats:italic>Mtb</jats:italic>-iNet was applied to data during clinical therapy of tuberculosis, it resulted in the most pronounced response and the weakest correlation. Correlation on dataset from patients with AIDS or malaria was stronger for T<jats:italic>Mtb</jats:italic>-iNet, indicating an involvement of T<jats:italic>Mtb</jats:italic>-iNet in these chronic human infections. Collectively, the significance of this work is twofold: (1) we disseminate a hub-based approach in generating a biologically meaningful and clinically useful signature; (2) using this approach we introduce a new network-based signature and demonstrate its promising applications in understanding host responses to infections.</jats:p>

Original publication




Journal article


BioMed Research International


Hindawi Limited

Publication Date





1 - 16