Inference of the genetic network regulating lateral root initiation in Arabidopsis thaliana

Regulation of gene expression is crucial for organism growth, and it is one of the challenges in Systems Biology to reconstruct the underlying regulatory biological networks from transcriptomic data. The formation of lateral roots in Arabidopsis thaliana is stimulated by a cascade of regulators of which only the interactions of its initial elements have been identified. Using simulated gene expression data with known network topology, we compare the performance of inference algorithms, based on different approaches, for which ready-to-use software is available. We show that their performance improves with the network size and the inclusion of mutants. We then analyse two sets of genes, whose activity is likely to be relevant to lateral root initiation in Arabidopsis, by integrating sequence analysis with the intersection of the results of the best performing methods on time series and mutants to infer their regulatory network. The methods applied capture known interactions between genes that are candidate regulators at early stages of development. The network inferred from genes significantly expressed during lateral root formation exhibits distinct scale-free, small world and hierarchical properties and the nodes with a high out-degree may warrant further investigation

Mathematical modelling plant signalling networks

During the last two decades, molecular genetic studies and the completion of the sequencing of the Arabidopsis thaliana genome have increased knowledge of hormonal regulation in plants. These signal transduction pathways act in concert through gene regulatory and signalling networks whose main components have begun to be elucidated. Our understanding of the resulting cellular processes is hindered by the complex, and sometimes counter-intuitive, dynamics of the networks, which may be interconnected through feedback controls and cross-regulation. Mathematical modelling provides a valuable tool to investigate such dynamics and to perform in silico experiments that may not be easily carried out in a laboratory. In this article, we firstly review general methods for modelling gene and signalling networks and their application in plants. We then describe specific models of hormonal perception and cross-talk in plants. This sub-cellular analysis paves the way for more comprehensive mathematical studies of hormonal transport and signalling in a multi-scale setting

Model-free reconstruction of neuronal network connectivity from calcium imaging signals

A systematic assessment of global neural network connectivity through direct electrophysiological assays has remained technically unfeasible even in dissociated neuronal cultures. We introduce an improved algorithmic approach based on Transfer Entropy to reconstruct approximations to network structural connectivities from network activity monitored through calcium fluorescence imaging. Based on information theory, our method requires no prior assumptions on the statistics of neuronal firing and neuronal connections. The performance of our algorithm is benchmarked on surrogate time-series of calcium fluorescence generated by the simulated dynamics of a network with known ground-truth topology. We find that the effective network topology revealed by Transfer Entropy depends qualitatively on the time-dependent dynamic state of the network (e.g., bursting or non-bursting). We thus demonstrate how conditioning with respect to the global mean activity improves the performance of our method. [...] Compared to other reconstruction strategies such as cross-correlation or Granger Causality methods, our method based on improved Transfer Entropy is remarkably more accurate. In particular, it provides a good reconstruction of the network clustering coefficient, allowing to discriminate between weakly or strongly clustered topologies, whereas on the other hand an approach based on cross-correlations would invariantly detect artificially high levels of clustering. Finally, we present the applicability of our method to real recordings of in vitro cortical cultures. We demonstrate that these networks are characterized by an elevated level of clustering compared to a random graph (although not extreme) and by a markedly non-local connectivity.Comment: 54 pages, 8 figures (+9 supplementary figures), 1 table; submitted for publicatio

Entering the blackboard jungle: canonical dysfunction in conscious machines

The central paradigm of Artificial Intelligence is rapidly shifting toward biological models for both robotic devices and systems performing such critical tasks as network management and process control. Here we apply recent mathematical analysis of the necessary conditions for consciousness in humans in an attempt to gain some understanding of the likely canonical failure modes inherent to a broad class of global workspace/blackboard machines designed to emulate biological functions. Similar problems are likely to confront other possible architectures, although their mathematical description may be far less straightforward

A Global Workspace perspective on mental disorders

Recent developments in Global Workspace theory suggest that human consciousness can suffer interpenetrating dysfunctions of mutual and reciprocal interaction with embedding environments which will have early onset and often insidiously staged developmental progression, possibly according to a cancer model. A simple rate distortion argument implies that, if an external information source is pathogenic, then sufficient exposure to it is sure to write a sufficiently accurate image of it on mind and body in a punctuated manner so as to initiate or promote simililarly progressively punctuated developmental disorder. There can, thus, be no simple, reductionist brain chemical 'bug in the program' whose 'fix' can fully correct the problem. On the contrary, the growth of an individual over the life course, and the inevitable contact with a toxic physical, social, or cultural environment, can be expected to initiate developmental problems which will become more intrusive over time, most obviously according to some damage accumulation model, but likely according to far more subtle, highly punctuated, schemes analogous to tumorigenesis. The key intervention, at the population level, is clearly to limit such exposures, a question of proper environmental sanitation, in a large sense, a matter of social justice which has long been understood to be determined almost entirely by the interactions of cultural trajectory, group power relations, and economic structure, with public policy. Intervention at the individual level appears limited to triggering or extending periods of remission, as is the case with most cancers

Biologically inspired distributed machine cognition: a new formal approach to hyperparallel computation

The irresistable march toward multiple-core chip technology presents currently intractable pdrogramming challenges. High level mental processes in many animals, and their analogs for social structures, appear similarly massively parallel, and recent mathematical models addressing them may be adaptable to the multi-core programming problem

The cultural epigenetics of psychopathology: The missing heritability of complex diseases found?

We extend a cognitive paradigm for gene expression based on the asymptotic limit theorems of information theory to the epigenetic epidemiology of mental disorders. In particular, we recognize the fundamental role culture plays in human biology, another heritage mechanism parallel to, and interacting with, the more familiar genetic and epigenetic systems. We do this via a model through which culture acts as another tunable epigenetic catalyst that both directs developmental trajectories, and becomes convoluted with individual ontology, via a mutually-interacting crosstalk mediated by a social interaction that is itself culturally driven. We call for the incorporation of embedding culture as an essential component of the epigenetic regulation of human mental development and its dysfunctions, bringing what is perhaps the central reality of human biology into the center of biological psychiatry. Current US work on gene-environment interactions in psychiatry must be extended to a model of gene-environment-culture interaction to avoid becoming victim of an extreme American individualism that threatens to create paradigms particular to that culture and that are, indeed, peculiar in the context of the world's cultures. The cultural and epigenetic systems of heritage may well provide the 'missing' heritability of complex diseases now under so much intense discussion