Sharif Digital Repository

Inferring the structure of molecular networks from time series protein or gene expression data provides valuable information about the complex biological processes of the cell. Causal network structure inference has been approached using different methods in the past. Most causal network inference techniques, such as Dynamic Bayesian Networks and ordinary differential equations, are limited by their computational complexity and thus make large scale inference infeasible. This is specifically true if a Bayesian framework is applied in order to deal with the unavoidable uncertainty about the correct model. We devise a novel Bayesian network reverse engineering approach using ordinary... 

Understanding the functionality of proteins has emerged as a critical problem in recent years due to significant roles of these macro-molecules in biological mechanisms. However, in-laboratory techniques for protein function prediction are not as efficient as methods developed and processed for protein sequencing. While more than 70 million protein sequences are available today, only the functionality of around one percent of them are known. These facts have encouraged researchers to develop computational methods to infer protein functionalities from their sequences. Gene Ontology is the most well-known database for protein functions which has a hierarchical structure, where deeper terms are... 

In this paper, the Extended Kalman filtering (EKF) approach has been used to infer gene regulatory networks using time-series gene expression data. Gene expression values are considered stochastic processes and the gene regulatory network, a dynamical nonlinear stochastic model. Using these values and a modified Kalman filtering approach, the model's parameters and consequently the interactions amongst genes are predicted. In this paper, each gene-gene interaction is modeled using a linear term, a nonlinear one, and a constant term. The linear and nonlinear term coefficients are included in the state vector together with the gene expressions' true values. Through the extended Kalman... 

It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was... 

Control problem in a biological system is the problem of finding an interventional policy for changing the state of the biological system from an undesirable state, e.g. disease, into a desirable healthy state. Boolean networks are utilized as a mathematical model for gene regulatory networks. This paper provides an algorithm to solve the control problem in Boolean networks. The proposed algorithm is implemented and applied on two biological systems: T-cell receptor network and Drosophila melanogaster network. Results show that the proposed algorithm works faster in solving the control problem over these networks, while having similar accuracy, in comparison to previous exact methods. Source... 

Background MicroRNAs (miRNAs) are frequently deregulated in various types of cancer. While antisense oligonucleotides are used to block oncomiRs, delivery of tumour-suppressive miRNAs holds great potential as a potent anti-cancer strategy. Here, we aim to determine, and functionally analyse, miRNAs that are lowly expressed in various types of tumour but abundantly expressed in multiple normal tissues. Methods The miRNA sequencing data of 14 cancer types were downloaded from the TCGA dataset. Significant differences in miRNA expression between tumor and normal samples were calculated using limma package (R programming). An adjusted p value < 0.05 was used to compare normal versus tumor miRNA...