NetControl4BioMed: a pipeline for biomedical data acquisition and analysis of network controllability

Abstract

BackgroundNetwork controllability focuses on discovering combinations of external interventions that can drive a biological system to a desired configuration. In practice, this approach translates into finding a combined multi-drug therapy in order to induce a desired response from a cell; this can lead to developments of novel therapeutic approaches for systemic diseases like cancer.ResultWe develop a novel bioinformatics data analysis pipeline called NetControl4BioMed based on the concept of target structural control of linear networks. Our pipeline generates novel molecular interaction networks by combining pathway data from various public databases starting from the user’s query. The pipeline then identifies a set of nodes that is enough to control a given, user-defined set of disease-specific essential proteins in the network, i.e., it is able to induce a change in their configuration from any initial state to any final state. We provide both the source code of the pipeline as well as an online web-service based on this pipeline http://combio.abo.fi/nc/net_control/remote_call.php.ConclusionThe pipeline can be used by researchers for controlling and better understanding of molecular interaction networks through combinatorial multi-drug therapies, for more efficient therapeutic approaches and personalised medicine.Electronic supplementary materialThe online version of this article (10.1186/s12859-018-2177-3) contains supplementary material, which is available to authorized users.

Xihuang Pill inhibits the development of DMBA combined estrogen and progesterone induced breast precancerous lesions rats by PI3K/AKT/mTOR signaling pathway

“…The phosphorylation of Serine 473 is necessary for the complete activation of AKT [25]. mTOR is a key downstream mediator in the PI3K/Akt/mTOR signaling pathway that plays a key role in regulating cell growth and hyperplasia during breast cancer development [26]. PTEN is a negative regulator in the PI3K-Akt-mTOR signaling pathway, could dephosphorylate the PI3K to down-regulate the activation of PI3K-Akt-mTOR pathway [27].…”

Network analytics for drug repurposing in COVID-19

“…Within this theoretical setting, the target controllability problem for a dynamical system defined by matrix A ∈ R n×n and target set T ⊆ V , |T | = l, is defined as follows: find the smallest m ≤ n and input set (a.k.a controller) I ⊆ V , |I| = m, such that for any x(0) ∈ R n and any α ∈ R l , there is an input vector u : R → R m such that the solution x of (1) eventually coincides with α on its T -components, i.e., C T x(τ ) = α, for some τ ≥ 0, where C T is the characteristic matrix of the target set T . Although the problem is known to be computationally hard [73], some efficient approximation algorithms were provided in [73,74].…”

Controllability of reaction systems

“…Some examples on applying the controllability problem in medicine are in [11,22,25,37] . Software for solving the controllability problem is available in [23,30].…”