Network estimation in State Space Model with L1-regularization constraint

Biological networks have arisen as an attractive paradigm of genomic science ever since the introduction of large scale genomic technologies which carried the promise of elucidating the relationship in functional genomics. Microarray technologies coupled with appropriate mathematical or statistical models have made it possible to identify dynamic regulatory networks or to measure time course of the expression level of many genes simultaneously. However one of the few limitations fall on the high-dimensional nature of such data coupled with the fact that these gene expression data are known to include some hidden process. In that regards, we are concerned with deriving a method for inferring a sparse dynamic network in a high dimensional data setting. We assume that the observations are noisy measurements of gene expression in the form of mRNAs, whose dynamics can be described by some unknown or hidden process. We build an input-dependent linear state space model from these hidden states and demonstrate how an incorporated $L_{1}$ regularization constraint in an Expectation-Maximization (EM) algorithm can be used to reverse engineer transcriptional networks from gene expression profiling data. This corresponds to estimating the model interaction parameters. The proposed method is illustrated on time-course microarray data obtained from a well established T-cell data. At the optimum tuning parameters we found genes TRAF5, JUND, CDK4, CASP4, CD69, and C3X1 to have higher number of inwards directed connections and FYB, CCNA2, AKT1 and CASP8 to be genes with higher number of outwards directed connections. We recommend these genes to be object for further investigation. Caspase 4 is also found to activate the expression of JunD which in turn represses the cell cycle regulator CDC2.Comment: arXiv admin note: substantial text overlap with arXiv:1308.359

Signal detection in extracellular neural ensemble recordings using higher criticism

Information processing in the brain is conducted by a concerted action of multiple neural populations. Gaining insights in the organization and dynamics of such populations can best be studied with broadband intracranial recordings of so-called extracellular field potential, reflecting neuronal spiking as well as mesoscopic activities, such as waves, oscillations, intrinsic large deflections, and multiunit spiking activity. Such signals are critical for our understanding of how neuronal ensembles encode sensory information and how such information is integrated in the large networks underlying cognition. The aforementioned principles are now well accepted, yet the efficacy of extracting information out of the complex neural data, and their employment for improving our understanding of neural networks, critically depends on the mathematical processing steps ranging from simple detection of action potentials in noisy traces - to fitting advanced mathematical models to distinct patterns of the neural signal potentially underlying intra-processing of information, e.g. interneuronal interactions. Here, we present a robust strategy for detecting signals in broadband and noisy time series such as spikes, sharp waves and multi-unit activity data that is solely based on the intrinsic statistical distribution of the recorded data. By using so-called higher criticism - a second-level significance testing procedure comparing the fraction of observed significances to an expected fraction under the global null - we are able to detect small signals in correlated noisy time-series without prior filtering, denoising or data regression. Results demonstrate the efficiency and reliability of the method and versatility over a wide range of experimental conditions and suggest the appropriateness of higher criticism to characterize neuronal dynamics without prior manipulation of the data

Neural Connectivity with Hidden Gaussian Graphical State-Model

The noninvasive procedures for neural connectivity are under questioning. Theoretical models sustain that the electromagnetic field registered at external sensors is elicited by currents at neural space. Nevertheless, what we observe at the sensor space is a superposition of projected fields, from the whole gray-matter. This is the reason for a major pitfall of noninvasive Electrophysiology methods: distorted reconstruction of neural activity and its connectivity or leakage. It has been proven that current methods produce incorrect connectomes. Somewhat related to the incorrect connectivity modelling, they disregard either Systems Theory and Bayesian Information Theory. We introduce a new formalism that attains for it, Hidden Gaussian Graphical State-Model (HIGGS). A neural Gaussian Graphical Model (GGM) hidden by the observation equation of Magneto-encephalographic (MEEG) signals. HIGGS is equivalent to a frequency domain Linear State Space Model (LSSM) but with sparse connectivity prior. The mathematical contribution here is the theory for high-dimensional and frequency-domain HIGGS solvers. We demonstrate that HIGGS can attenuate the leakage effect in the most critical case: the distortion EEG signal due to head volume conduction heterogeneities. Its application in EEG is illustrated with retrieved connectivity patterns from human Steady State Visual Evoked Potentials (SSVEP). We provide for the first time confirmatory evidence for noninvasive procedures of neural connectivity: concurrent EEG and Electrocorticography (ECoG) recordings on monkey. Open source packages are freely available online, to reproduce the results presented in this paper and to analyze external MEEG databases