No Arabic abstract
We analyze gene co-expression network under the random matrix theory framework. The nearest neighbor spacing distribution of the adjacency matrix of this network follows Gaussian orthogonal statistics of random matrix theory (RMT). Spectral rigidity test follows random matrix prediction for a certain range, and deviates after wards. Eigenvector analysis of the network using inverse participation ratio (IPR) suggests that the statistics of bulk of the eigenvalues of network is consistent with those of the real symmetric random matrix, whereas few eigenvalues are localized. Based on these IPR calculations, we can divide eigenvalues in three sets; (A) The non-degenerate part that follows RMT. (B) The non-degenerate part, at both ends and at intermediate eigenvalues, which deviate from RMT and expected to contain information about {it important nodes} in the network. (C) The degenerate part with $zero$ eigenvalue, which fluctuates around RMT predicted value. We identify nodes corresponding to the dominant modes of the corresponding eigenvectors and analyze their structural properties.
We analyze the gene expression data of Zebrafish under the combined framework of complex networks and random matrix theory. The nearest neighbor spacing distribution of the corresponding matrix spectra follows random matrix predictions of Gaussian orthogonal statistics. Based on the eigenvector analysis we can divide the spectra into two parts, first part for which the eigenvector localization properties match with the random matrix theory predictions, and the second part for which they show deviation from the theory and hence are useful to understand the system dependent properties. Spectra with the localized eigenvectors can be characterized into three groups based on the eigenvalues. We explore the position of localized nodes from these different categories. Using an overlap measure, we find that the top contributing nodes in the different groups carry distinguished structural features. Furthermore, the top contributing nodes of the different localized eigenvectors corresponding to the lower eigenvalue regime form different densely connected structure well separated from each other. Preliminary biological interpretation of the genes, associated with the top contributing nodes in the localized eigenvectors, suggests that the genes corresponding to same vector share common features.
Inferring functional relationships within complex networks from static snapshots of a subset of variables is a ubiquitous problem in science. For example, a key challenge of systems biology is to translate cellular heterogeneity data obtained from single-cell sequencing or flow-cytometry experiments into regulatory dynamics. We show how static population snapshots of co-variability can be exploited to rigorously infer properties of gene expression dynamics when gene expression reporters probe their upstream dynamics on separate time-scales. This can be experimentally exploited in dual-reporter experiments with fluorescent proteins of unequal maturation times, thus turning an experimental bug into an analysis feature. We derive correlation conditions that detect the presence of closed-loop feedback regulation in gene regulatory networks. Furthermore, we show how genes with cell-cycle dependent transcription rates can be identified from the variability of co-regulated fluorescent proteins. Similar correlation constraints might prove useful in other areas of science in which static correlation snapshots are used to infer causal connections between dynamically interacting components.
The phenotype of any organism on earth is, in large part, the consequence of interplay between numerous gene products encoded in the genome, and such interplay between gene products affects the evolutionary fate of the genome itself through the resulting phenotype. In this regard, contemporary genomes can be used as molecular records that reveal associations of various genes working in their natural lifestyles. By analyzing thousands of orthologs across ~600 bacterial species, we constructed a map of gene-gene co-occurrence across much of the sequenced biome. If genes preferentially co-occur in the same organisms, they were called herein correlogs; in the opposite case, called anti-correlogs. To quantify correlogy and anti-correlogy, we alleviated the contribution of indirect correlations between genes by adapting ideas developed for reverse engineering of transcriptional regulatory networks. Resultant correlogous associations are highly enriched for physically interacting proteins and for co-expressed transcripts, clearly differentiating a subgroup of functionally-obligatory protein interactions from conditional or transient interactions. Other biochemical and phylogenetic properties were also found to be reflected in correlogous and anti-correlogous relationships. Additionally, our study elucidates the global organization of the gene association map, in which various modules of correlogous genes are strikingly interconnected by anti-correlogous crosstalk between the modules. We then demonstrate the effectiveness of such associations along different domains of life and environmental microbial communities. These phylogenetic profiling approaches infer functional coupling of genes regardless of mechanistic details, and may be useful to guide exogenous gene import in synthetic biology.
According to the `ceRNA hypothesis, microRNAs (miRNAs) may act as mediators of an effective positive interaction between long coding or non-coding RNA molecules, carrying significant potential implications for a variety of biological processes. Here, inspired by recent work providing a quantitative description of small regulatory elements as information-conveying channels, we characterize the effectiveness of miRNA-mediated regulation in terms of the optimal information flow achievable between modulator (transcription factors) and target nodes (long RNAs). Our findings show that, while a sufficiently large degree of target derepression is needed to activate miRNA-mediated transmission, (a) in case of differential mechanisms of complex processing and/or transcriptional capabilities, regulation by a post-transcriptional miRNA-channel can outperform that achieved through direct transcriptional control; moreover, (b) in the presence of large populations of weakly interacting miRNA molecules the extra noise coming from titration disappears, allowing the miRNA-channel to process information as effectively as the direct channel. These observations establish the limits of miRNA-mediated post-transcriptional cross-talk and suggest that, besides providing a degree of noise buffering, this type of control may be effectively employed in cells both as a failsafe mechanism and as a preferential fine tuner of gene expression, pointing to the specific situations in which each of these functionalities is maximized.
We assess the impact of cell cycle noise on gene circuit dynamics. For bistable genetic switches and excitable circuits, we find that transitions between metastable states most likely occur just after cell division and that this concentration effect intensifies in the presence of transcriptional delay. We explain this concentration effect with a 3-states stochastic model. For genetic oscillators, we quantify the temporal correlations between daughter cells induced by cell division. Temporal correlations must be captured properly in order to accurately quantify noise sources within gene networks.