A Fast Reconstruction Algorithm for Gene Networks

This paper deals with gene networks whose dynamics is assumed to be generated by a continuous-time, linear, time invariant, finite dimensional system (LTI) at steady state. In particular, we deal with the problem of network reconstruction in the typical practical situation in which the number of available data is largely insufficient to uniquely determine the network. In order to try to remove this ambiguity, we will exploit the biologically a priori assumption of network sparseness, and propose a new algorithm for network reconstruction having a very low computational complexity (linear in the number of genes) so to be able to deal also with very large networks (say, thousands of genes). Its performances are also tested both on artificial data (generated with linear models) and on real data obtained by Gardner et al. from the SOS pathway in Escherichia coli.Comment: 12 pages, 3 figure

PVT1: a rising star among oncogenic long non-coding RNAs

It is becoming increasingly clear that short and long noncoding RNAs critically participate in the regulation of cell growth, differentiation, and (mis)function. However, while the functional characterization of short non-coding RNAs has been reaching maturity, there is still a paucity of well characterized long noncoding RNAs, even though large studies in recent years are rapidly increasing the number of annotated ones. The long noncoding RNA PVT1 is encoded by a gene that has been long known since it resides in the well-known cancer risk region 8q24. However, a couple of accidental concurrent conditions have slowed down the study of this gene, that is, a preconception on the primacy of the protein-coding over noncoding RNAs and the prevalent interest in its neighbor MYC oncogene. Recent studies have brought PVT1 under the spotlight suggesting interesting models of functioning, such as competing endogenous RNA activity and regulation of protein stability of important oncogenes, primarily of the MYC oncogene. Despite some advancements in modelling the PVT1 role in cancer, there are many questions that remain unanswered concerning the precise molecular mechanisms underlying its functioning

Learning-based predictive control for linear systems: a unitary approach

A comprehensive approach addressing identification and control for learningbased Model Predictive Control (MPC) for linear systems is presented. The design technique yields a data-driven MPC law, based on a dataset collected from the working plant. The method is indirect, i.e. it relies on a model learning phase and a model-based control design one, devised in an integrated manner. In the model learning phase, a twofold outcome is achieved: first, different optimal p-steps ahead prediction models are obtained, to be used in the MPC cost function; secondly, a perturbed state-space model is derived, to be used for robust constraint satisfaction. Resorting to Set Membership techniques, a characterization of the bounded model uncertainties is obtained, which is a key feature for a successful application of the robust control algorithm. In the control design phase, a robust MPC law is proposed, able to track piece-wise constant reference signals, with guaranteed recursive feasibility and convergence properties. The controller embeds multistep predictors in the cost function, it ensures robust constraints satisfaction thanks to the learnt uncertainty model, and it can deal with possibly unfeasible reference values. The proposed approach is finally tested in a numerical example

Network-based approaches to explore complex biological systems towards network medicine

Network medicine relies on different types of networks: from the molecular level of protein–protein interactions to gene regulatory network and correlation studies of gene expression. Among network approaches based on the analysis of the topological properties of protein–protein interaction (PPI) networks, we discuss the widespread DIAMOnD (disease module detection) algorithm. Starting from the assumption that PPI networks can be viewed as maps where diseases can be identified with localized perturbation within a specific neighborhood (i.e., disease modules), DIAMOnD performs a systematic analysis of the human PPI network to uncover new disease-associated genes by exploiting the connectivity significance instead of connection density. The past few years have witnessed the increasing interest in understanding the molecular mechanism of post-transcriptional regulation with a special emphasis on non-coding RNAs since they are emerging as key regulators of many cellular processes in both physiological and pathological states. Recent findings show that coding genes are not the only targets that microRNAs interact with. In fact, there is a pool of different RNAs—including long non-coding RNAs (lncRNAs) —competing with each other to attract microRNAs for interactions, thus acting as competing endogenous RNAs (ceRNAs). The framework of regulatory networks provides a powerful tool to gather new insights into ceRNA regulatory mechanisms. Here, we describe a data-driven model recently developed to explore the lncRNA-associated ceRNA activity in breast invasive carcinoma. On the other hand, a very promising example of the co-expression network is the one implemented by the software SWIM (switch miner), which combines topological properties of correlation networks with gene expression data in order to identify a small pool of genes—called switch genes—critically associated with drastic changes in cell phenotype. Here, we describe SWIM tool along with its applications to cancer research and compare its predictions with DIAMOnD disease genes

Stochastic Modeling of Expression Kinetics Identifies Messenger Half-Lives and Reveals Sequential Waves of Co-ordinated Transcription and Decay

The transcriptome in a cell is finely regulated by a large number of molecular mechanisms able to control the balance between mRNA production and degradation. Recent experimental findings have evidenced that fine and specific regulation of degradation is needed for proper orchestration of a global cell response to environmental conditions. We developed a computational technique based on stochastic modeling, to infer condition-specific individual mRNA half-lives directly from gene expression time-courses. Predictions from our method were validated by experimentally measured mRNA decay rates during the intraerythrocytic developmental cycle of Plasmodium falciparum. We then applied our methodology to publicly available data on the reproductive and metabolic cycle of budding yeast. Strikingly, our analysis revealed, in all cases, the presence of periodic changes in decay rates of sequentially induced genes and co-ordination strategies between transcription and degradation, thus suggesting a general principle for the proper coordination of transcription and degradation machinery in response to internal and/or external stimuli. Citation: Cacace F, Paci P, Cusimano V, Germani A, Farina L (2012) Stochastic Modeling of Expression Kinetics Identifies Messenger Half-Lives and Reveals Sequential Waves of Co-ordinated Transcription and Decay. PLoS Comput Biol 8(11): e1002772. doi:10.1371/journal.pcbi.100277

Image fusion techniqes for remote sensing applications

Image fusion refers to the acquisition, processing and synergistic combination of information provided by various sensors or by the same sensor in many measuring contexts. The aim of this survey paper is to describe three typical applications of data fusion in remote sensing. The first study case considers the problem of the Synthetic Aperture Radar (SAR) Interferometry, where a pair of antennas are used to obtain an elevation map of the observed scene; the second one refers to the fusion of multisensor and multitemporal (Landsat Thematic Mapper and SAR) images of the same site acquired at different times, by using neural networks; the third one presents a processor to fuse multifrequency, multipolarization and mutiresolution SAR images, based on wavelet transform and multiscale Kalman filter. Each study case presents also results achieved by the proposed techniques applied to real data

SWIM: A computational tool to unveiling crucial nodes in complex biological networks

SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. Specifically, SWIM allows unearthing the existence of a new class of hubs, called "fight-club hubs", characterized by a marked negative correlation with their first nearest neighbors. Among them, a special subset of genes, called "switch genes", appears to be characterized by an unusual pattern of intra- and inter-module connections that confers them a crucial topological role, interestingly mirrored by the evidence of their clinic-biological relevance. Here, we applied SWIM to a large panel of cancer datasets from The Cancer Genome Atlas, in order to highlight switch genes that could be critically associated with the drastic changes in the physiological state of cells or tissues induced by the cancer development. We discovered that switch genes are found in all cancers we studied and they encompass protein coding genes and non-coding RNAs, recovering many known key cancer players but also many new potential biomarkers not yet characterized in cancer context. Furthermore, SWIM is amenable to detect switch genes in different organisms and cell conditions, with the potential to uncover important players in biologically relevant scenarios, including but not limited to human cancer

Computational analysis identifies a sponge interaction network between long non-coding RNAs and messenger RNAs in human breast cancer

Background: Non-coding RNAs (ncRNAs) are emerging as key regulators of many cellular processes in both physiological and pathological states. Moreover, the constant discovery of new non-coding RNA species suggests that the study of their complex functions is still in its very early stages. This variegated class of RNA species encompasses the well-known microRNAs (miRNAs) and the most recently acknowledged long non-coding RNAs (lncRNAs). Interestingly, in the last couple of years, a few studies have shown that some lncRNAs can act as miRNA sponges, i.e. as competing endogenous RNAs (ceRNAs), able to reduce the amount of miRNAs available to target messenger RNAs (mRNAs).Results: We propose a computational approach to explore the ability of lncRNAs to act as ceRNAs by protecting mRNAs from miRNA repression. A seed match analysis was performed to validate the underlying regression model. We built normal and cancer networks of miRNA-mediated sponge interactions (MMI-networks) using breast cancer expression data provided by The Cancer Genome Atlas.Conclusions: Our study highlights a marked rewiring in the ceRNA program between normal and pathological breast tissue, documented by its " on/off" switch from normal to cancer, and vice-versa. This mutually exclusive activation confers an interesting character to ceRNAs as potential oncosuppressive, or oncogenic, protagonists in cancer. At the heart of this phenomenon is the lncRNA PVT1, as illustrated by both the width of its antagonist mRNAs in normal-MMI-network, and the relevance of the latter in breast cancer. Interestingly, PVT1 revealed a net binding preference towards the mir-200 family as the bone of contention with its rival mRNAs. © 2014 Paci et al.; licensee BioMed Central Ltd