Biomedical subjects

Isaac Meilijson

Publications and source records attributed to Isaac Meilijson.

8 recordsLinked to original sources

PubMed2006

Gene expression of Caenorhabditis elegans neurons carries information on their synaptic connectivity.

The claim that genetic properties of neurons significantly influence their synaptic network structure is a common notion in neuroscience. The nematode Caenorhabditis elegans provides an exciting opportunity to approach this question in a large-scale quantitative manner. Its synaptic connectivity network has been identified, and, combined with cellular studies, we currently have characteristic connectivity and gene expression signatures for most of its neurons. By using two complementary analysis assays we show that the expression signature of a neuron carries significant information about its synaptic connectivity signature, and identify a list of putative genes predicting neural connectivity. The current study rigorously quantifies the relation between gene expression and synaptic connectivity signatures in the C. elegans nervous system and identifies subsets of neurons where this relation is highly marked. The results presented and the genes identified provide a promising starting point for further, more detailed computational and experimental investigations.

Animals↗

PubMed2006

Multiple knockout analysis of genetic robustness in the yeast metabolic network.

Genetic robustness characterizes the constancy of the phenotype in face of heritable perturbations. Previous investigations have used comprehensive single and double gene knockouts to study gene essentiality and pairwise gene interactions in the yeast Saccharomyces cerevisiae. Here we conduct an in silico multiple knockout investigation of a flux balance analysis model of the yeast's metabolic network. Cataloging gene sets that provide mutual functional backup, we identify sets of up to eight interacting genes and characterize the 'k robustness' (the depth of backup interactions) of each gene. We find that 74% (360) of the metabolic genes participate in processes that are essential to growth in a standard laboratory environment, compared with only 13% previously found to be essential using single knockouts. The genes' k robustness is shown to be a solid indicator of their biological buffering capacity and is correlated with both the genes' environmental specificity and their evolutionary retention.

Computer Simulation↗

PubMed2006

Axiomatic scalable neurocontroller analysis via the Shapley value.

One of the major challenges in the field of neurally driven evolved autonomous agents is deciphering the neural mechanisms underlying their behavior. Aiming at this goal, we have developed the multi-perturbation Shapley value analysis (MSA)--the first axiomatic and rigorous method for deducing causal function localization from multiple-perturbation data, substantially improving on earlier approaches. Based on fundamental concepts from game theory, the MSA provides a formal way of defining and quantifying the contributions of network elements, as well as the functional interactions between them. The previously presented versions of the MSA require full knowledge (or at least an approximation) of the network's performance under all possible multiple perturbations, limiting their applicability to systems with a small number of elements. This article focuses on presenting new scalable MSA variants, allowing for the analysis of large complex networks in an efficient manner, including large-scale neurocontrollers. The successful operation of the MSA along with the new variants is demonstrated in the analysis of several neurocontrollers solving a food foraging task, consisting of up to 100 neural elements.

Models, Statistical↗

PubMed2005

Quantitative analysis of genetic and neuronal multi-perturbation experiments.

Perturbation studies, in which functional performance is measured after deletion, mutation, or lesion of elements of a biological system, have been traditionally employed in many fields in biology. The vast majority of these studies have been qualitative and have employed single perturbations, often resulting in little phenotypic effect. Recently, newly emerging experimental techniques have allowed researchers to carry out concomitant multi-perturbations and to uncover the causal functional contributions of system elements. This study presents a rigorous and quantitative multi-perturbation analysis of gene knockout and neuronal ablation experiments. In both cases, a quantification of the elements' contributions, and new insights and predictions, are provided. Multi-perturbation analysis has a potentially wide range of applications and is gradually becoming an essential tool in biology.

Algorithms↗

PubMed2004

Fair attribution of functional contribution in artificial and biological networks.

This letter presents the multi-perturbation Shapley value analysis (MSA), an axiomatic, scalable, and rigorous method for deducing causal function localization from multiple perturbations data. The MSA, based on fundamental concepts from game theory, accurately quantifies the contributions of network elements and their interactions, overcoming several shortcomings of previous function localization approaches. Its successful operation is demonstrated in both the analysis of a neurophysiological model and of reversible deactivation data. The MSA has a wide range of potential applications, including the analysis of reversible deactivation experiments, neuronal laser ablations, and transcranial magnetic stimulation "virtual lesions," as well as in providing insight into the inner workings of computational models of neurophysiological systems.

Algorithms↗

PubMed2003

Controlled analysis of neurocontrollers with informational lesioning.

How does one aim to understand neural information processing? One of the difficult first challenges is to identify the roles of the network's elements. To this end a functional contribution analysis (FCA) method has been developed and applied for studying the neurocontrollers of evolutionary autonomous agents (EAAs). The FCA processes data composed of multiple lesion experiments and the corresponding performance levels that the agent obtains under these lesions. It calculates the contribution values (CVs) of the network's elements such that the ability to predict the agent's performance under new, unseen lesions is maximized. Previous analysis has found a strong dependence of the CVs and the prediction error on the specific type of lesioning method used, i.e. on the way in which the activity of lesioned neurons is disrupted. We present a new, informational lesioning method (ILM), which views a lesion as a noisy channel and applies a controlled lesion to the network by varying the lesioning level from large to arbitrarily small magnitudes. Studying the ILM within the FCA framework, our main results are threefold: first, that lower lesioning levels permit more accurate FCA predictions; second, that the usage of minute ILM lesioning levels can uncover the long-term effects of elements on the network's functioning; and third, that as the lesioning level decreases, the CVs tend to approach limit values, reflecting the importance of these elements in the intact, normal-functioning neurocontroller.

Adaptation, Physiological↗

PubMed2003

Localization of function via lesion analysis.

This article presents a general approach for employing lesion analysis to address the fundamental challenge of localizing functions in a neural system. We describe functional contribution analysis (FCA), which assigns contribution values to the elements of the network such that the ability to predict the network's performance in response to multilesions is maximized. The approach is thoroughly examined on neurocontroller networks of evolved autonomous agents. The FCA portrays a stable set of neuronal contributions and accurate multilesion predictions that are significantly better than those obtained based on the classical single lesion approach. It is also used for a detailed synaptic analysis of the neurocontroller connectivity network, delineating its main functional backbone. The FCA provides a quantitative way of measuring how the network functions are localized and distributed among its elements. Our results question the adequacy of the classical single lesion analysis traditionally used in neuroscience and show that using lesioning experiments to decipher even simple neuronal systems requires a more rigorous multilesion analysis.

Algorithms↗

PubMed2003

High-dimensional analysis of evolutionary autonomous agents.

This article presents a new approach to the important challenge of localizing function in a neurocontroller. The approach is based on the basic functional contribution analysis (FCA) presented earlier, which assigns contribution values to the elements of the network, such that the ability to predict the network's performance in response to multi-unit lesions is maximized. These contribution values quantify the importance of each element to the tasks the agent performs. Here we present a generalization of the basic FCA to high-dimensional analysis, using high-order compound elements. Such elements are composed of conjunctions of simple elements. Their usage enables the explicit expression of sets of neurons or synapses whose contributions are interdependent, a prerequisite for localizing the function of complex neurocontrollers. High-dimensional FCA is shown to significantly improve on the accuracy of the basic analysis, to provide new insights concerning the main subsets of simple elements in the network that interact in a complex nonlinear manner, and to systematically reveal the types of interactions that characterize the evolved neurocontroller.

Artificial Intelligence↗