Understanding and Predicting Biological Networks Using Linear System Identi cation

in Kulkarni, V.; Stan, G.; Raman, K. (Eds.) A Systems Theoretic Approach to Systems and Synthetic Biology I: Models and System Characterizations (2014)

Dynamical structure function identifiability conditions enabling signal structure reconstruction

in The proceedings of the 51st IEEE Conference on Decision and Control (CDC) (2012, December)

Networks of controlled dynamical systems exhibit a variety of interconnection patterns that could be interpreted as the structure of the system. One such interpretation of system structure is a system's ... [more ▼]

Networks of controlled dynamical systems exhibit a variety of interconnection patterns that could be interpreted as the structure of the system. One such interpretation of system structure is a system's signal structure, characterized as the open-loop causal dependencies among manifest variables and represented by its dynamical structure function. Although this notion of structure is among the weakest available, previous work has shown that if no a priori structural information is known about the system, not even the Boolean structure of the dynamical structure function is identifiable. Consequently, one method previously suggested for obtaining the necessary a priori structural information is to leverage knowledge about target specificity of the controlled inputs. This work extends these results to demonstrate precisely the a priori structural information that is both necessary and sufficient to reconstruct the network from input-output data. This extension is important because it significantly broadens the applicability of the identifiability conditions, enabling the design of network reconstruction experiments that were previously impossible due to practical constraints on the types of actuation mechanisms available to the engineer or scientist. The work is motivated by the proteomics problem of reconstructing the Per-Arnt-Sim Kinase pathway used in the metabolism of sugars. [less ▲]

Comparing the MicroRNA Spectrum between Serum and Plasma

in PLoS ONE (2012), 7(7), 41561

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate various biological processes, primarily through interaction with messenger RNAs. The levels of specific, circulating miRNAs in blood have been ... [more ▼]

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate various biological processes, primarily through interaction with messenger RNAs. The levels of specific, circulating miRNAs in blood have been shown to associate with various pathological conditions including cancers. These miRNAs have great potential as biomarkers for various pathophysiological conditions. In this study we focused on different sample types’ effects on the spectrum of circulating miRNA in blood. Using serum and corresponding plasma samples from the same individuals, we observed higher miRNA concentrations in serum samples compared to the corresponding plasma samples. The difference between serum and plasma miRNA concentration showed some associations with miRNA from platelets, which may indicate that the coagulation process may affect the spectrum of extracellular miRNA in blood. Several miRNAs also showed platform dependent variations in measurements. Our results suggest that there are a number of factors that might affect the measurement of circulating miRNA concentration. Caution must be taken when comparing miRNA data generated from different sample types or measurement platforms [less ▲]

Reconstruction of arbitrary biochemical reaction networks: A compressive sensing approach

in The proceedings of the 51st IEEE Conference on Decision and Control (2012)

Reconstruction of biochemical reaction networks (BRN) and genetic regulatory networks (GRN) in particular is a central topic in systems biology which raises crucial theoretical challenges in system ... [more ▼]

Reconstruction of biochemical reaction networks (BRN) and genetic regulatory networks (GRN) in particular is a central topic in systems biology which raises crucial theoretical challenges in system identification. Nonlinear Ordinary Differential Equations (ODEs) that involve polynomial and rational functions are typically used to model biochemical reaction networks. Such nonlinear models make the problem of determining the connectivity of biochemical networks from time-series experimental data quite difficult. In this paper, we present a network reconstruction algorithm that can deal with ODE model descriptions containing polynomial and rational functions. Rather than identifying the parameters of linear or nonlinear ODEs characterised by pre-defined equation structures, our methodology allows us to determine the nonlinear ODEs structure together with their associated parameters. To solve the network reconstruction problem, we cast it as a compressive sensing (CS) problem and use sparse Bayesian learning (SBL) algorithms as a computationally efficient and robust way to obtain its solution. [less ▲]

The complex exogenous RNA spectra in human plasma: an interface with human gut biota?

in PLoS ONE (2012), 7(12),

Human plasma has long been a rich source for biomarker discovery. It has recently become clear that plasma RNA molecules, such as microRNA, in addition to proteins are common and can serve as biomarkers ... [more ▼]

Human plasma has long been a rich source for biomarker discovery. It has recently become clear that plasma RNA molecules, such as microRNA, in addition to proteins are common and can serve as biomarkers. Surveying human plasma for microRNA biomarkers using next generation sequencing technology, we observed that a significant fraction of the circulating RNA appear to originate from exogenous species. With careful analysis of sequence error statistics and other controls, we demonstrated that there is a wide range of RNA from many different organisms, including bacteria and fungi as well as from other species. These RNAs may be associated with protein, lipid or other molecules protecting them from RNase activity in plasma. Some of these RNAs are detected in intracellular complexes and may be able to influence cellular activities under in vitro conditions. These findings raise the possibility that plasma RNAs of exogenous origin may serve as signaling molecules mediating for example the human-microbiome interaction and may affect and/or indicate the state of human health [less ▲]

Minimal-time uncertain output final value of unknown DT-LTI systems with application to the decentralised network consensus problem

Scientific Conference (2010)

Robust dynamical network structure reconstruction

Scientific Conference (2010)

Motivated by biological applications, this paper addresses the problem of network reconstruction from data. Previous work has shown necessary and sufficient conditions for network reconstruction of noise ... [more ▼]

Motivated by biological applications, this paper addresses the problem of network reconstruction from data. Previous work has shown necessary and sufficient conditions for network reconstruction of noise-free LTI systems. This paper assumes that the conditions for network reconstruction have been met but here we additionally take into account noise and unmodelled dynamics (including nonlinearities). Algorithms are therefore proposed to reconstruct dynamical (Boolean) network structure from time-series (steady-state) data respectively in presence of noise and nonlinearities. In order to identify the network structure that generated the data, we compute the smallest distances between the measured data and the data that would have been generated by particular Boolean structures. Information criteria and optimisation technique balancing such distance and model complexity are introduced to search for the true structure. We conclude with biologically-inspired network reconstruction examples which include noise and nonlinearities. [less ▲]

Minimal dynamical structure realisations with application to network reconstruction from data

in The proceedings of the Joint 48th IEEE Conference on Decision and Control and 28th Chinese Control Conference (2009)

Network reconstruction, i.e., obtaining network structure from data, is a central theme in systems biology, economics, and engineering. Previous work introduced dynamical structure functions as a tool for ... [more ▼]

Network reconstruction, i.e., obtaining network structure from data, is a central theme in systems biology, economics, and engineering. Previous work introduced dynamical structure functions as a tool for posing and solving the problem of network reconstruction between measured states. While recovering the network structure between hidden states is not possible since they are not measured, in many situations it is important to estimate the number of hidden states in order to understand the complexity of the network under investigation and help identify potential targets for measurements. Estimating the number of hidden states is also crucial to obtain the simplest state-space model that captures the network structure and is coherent with the measured data. This paper characterises minimal order state-space realisations that are consistent with a given dynamical structure function by exploring properties of dynamical structure functions and developing algorithms to explicitly obtain a minimal reconstruction. [less ▲]