Fig 1.
A schematic diagram of diversified control paths.
(a): a linear dynamic system with adjacency matrix A and input matrix B. (b): the Kalman’s controllability rank condition, if rank(QC) = n, this system is controllable. (c): for the underlying network, propose a maximum-matching set (MMSet) to assess the structural controllability. Links of the MMSet are highlighted by red. (d): for a network G(A), differentiated MMSet M1 and M2, marked by red, construct diversified control path sets. Disease genes are marked by purple and their perturbation ranges are indicated by shadow areas.
Fig 2.
The perturbation influences of disease genes of the Tuberculosis (MIM:107470).
(a): A CPSet of the partial human regulatory network, the MMSet links are highlighted by red, the disease gene IFNGR1 and IFNG are marked by purple, their perturbation ranges are circled with red and blue dotted lines respectively. (b): Another differentiated CPSet. (c): the perturbation influences of IFNGR1 and IFNG are marked by red and blue shadow respectively.
Table 1.
Instances for the perturbation influence of disease gene.
Table 2.
The ranks of known disease genes for three instances.
Table 3.
The top ranked candidate genes for some instances.
Fig 3.
Comparison in performance between our method and PRINCE.
A plot of recall versus rank threshold, rank threshold k% means that the gene was ranked within top k%.
Table 4.
Enrichment analysis of causal genes in Alzheimer Disease.
Table 5.
Enrichment analysis of causal genes in Diabetes Mellitus, Type 2.
Table 6.
Enrichment analysis of causal genes in Leukemia.
Fig 4.
Analysis results for robustness of our method.
(a) The AUC of 2-fold cross validation for prioritization of oncogenes in the cancer signaling map. (b) The AUC of 5-fold cross validation for prioritization of oncogenes in the cancer signaling map. (c) The AUC of 10-fold cross validation for prioritization of oncogenes in the cancer signaling map. (d) The stability of perturbation influence of the regulatory network. (e) The stability of perturbation influence of the cancer signaling map.
Fig 5.
Sketch of prediction results for Breast cancer in Cancer Signaling Map.
5 known disease genes are highlighted by red color, 15 top ranked potential causal genes are highlighted by magenta color and the genes in the diversified control paths of disease genes are highlighted by purple color.
Table 7.
The top ranked candidate genes for Breast cancer in Cancer Signaling Map.