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

Quantifying the Structure of Misfolded Proteins Using Graph Theory

The structure of a protein molecule is highly correlated to its function. Some diseases such as cystic fibrosis are the result of a change in the structure of a protein so that this change interferes or inhibits its function. Often these changes in structure are caused by a misfolding of the protein molecule. To assist computational biologists, there is a database of proteins together with their misfolded versions, called decoys, that can be used to test the accuracy of protein structure prediction algorithms. In our work we use a nested graph model to quantify a selected set of proteins that have two single misfold decoys. The graph theoretic model used is a three tiered nested graph. Measures based on the vertex weights are calculated and we compare the quantification of the proteins with their decoys. Our method is able to separate the misfolded proteins from the correctly folded proteins

Learning mutational graphs of individual tumour evolution from single-cell and multi-region sequencing data

Background. A large number of algorithms is being developed to reconstruct evolutionary models of individual tumours from genome sequencing data. Most methods can analyze multiple samples collected either through bulk multi-region sequencing experiments or the sequencing of individual cancer cells. However, rarely the same method can support both data types. Results. We introduce TRaIT, a computational framework to infer mutational graphs that model the accumulation of multiple types of somatic alterations driving tumour evolution. Compared to other tools, TRaIT supports multi-region and single-cell sequencing data within the same statistical framework, and delivers expressive models that capture many complex evolutionary phenomena. TRaIT improves accuracy, robustness to data-specific errors and computational complexity compared to competing methods. Conclusions. We show that the application of TRaIT to single-cell and multi-region cancer datasets can produce accurate and reliable models of single-tumour evolution, quantify the extent of intra-tumour heterogeneity and generate new testable experimental hypotheses

Element-centric clustering comparison unifies overlaps and hierarchy

Clustering is one of the most universal approaches for understanding complex data. A pivotal aspect of clustering analysis is quantitatively comparing clusterings; clustering comparison is the basis for many tasks such as clustering evaluation, consensus clustering, and tracking the temporal evolution of clusters. In particular, the extrinsic evaluation of clustering methods requires comparing the uncovered clusterings to planted clusterings or known metadata. Yet, as we demonstrate, existing clustering comparison measures have critical biases which undermine their usefulness, and no measure accommodates both overlapping and hierarchical clusterings. Here we unify the comparison of disjoint, overlapping, and hierarchically structured clusterings by proposing a new element-centric framework: elements are compared based on the relationships induced by the cluster structure, as opposed to the traditional cluster-centric philosophy. We demonstrate that, in contrast to standard clustering similarity measures, our framework does not suffer from critical biases and naturally provides unique insights into how the clusterings differ. We illustrate the strengths of our framework by revealing new insights into the organization of clusters in two applications: the improved classification of schizophrenia based on the overlapping and hierarchical community structure of fMRI brain networks, and the disentanglement of various social homophily factors in Facebook social networks. The universality of clustering suggests far-reaching impact of our framework throughout all areas of science

Mean-Field-Type Games in Engineering

A mean-field-type game is a game in which the instantaneous payoffs and/or the state dynamics functions involve not only the state and the action profile but also the joint distributions of state-action pairs. This article presents some engineering applications of mean-field-type games including road traffic networks, multi-level building evacuation, millimeter wave wireless communications, distributed power networks, virus spread over networks, virtual machine resource management in cloud networks, synchronization of oscillators, energy-efficient buildings, online meeting and mobile crowdsensing.Comment: 84 pages, 24 figures, 183 references. to appear in AIMS 201

The past and future of terrorism research

Este artículo destaca cinco áreas donde el análisis económico del terrorismo ha tenido mayor relevancia en las políticas de los últimos 30 años. Estas áreas son la evaluación de la efectividad de las acciones contra el terrorismo, la identificación de las causas del terrorismo, la medición de las consecuencias económicas del terrorismo, el análisis de la dinámica de las series temporales de actos terroristas y la formulación de representaciones del terrorismo basadas en la teoría de juegos. La principal novedad del artículo es que sintetiza investigaciones anteriores e identifica las cuestiones más importantes en las políticas que requieren un análisis adicional. Estas cuestiones permiten entender cómo operan las redes globales de terrorismo, evaluar los resultados de las estrategias antiterroristas y de formas alternativas de cooperación internacional e investigar los aspectos estratégicos del terrorismo de suicidas. Se ofrece un procedimiento para tratar cada una de estas políticas.terrorismo, contraterrorismo, análisis coste beneficio, teoría de juegos, efectividad de las políticas, consecuencias económicas.