arXiv subjects

M. Cosentino Lagomarsino

Publications and source records attributed to M. Cosentino Lagomarsino.

At least 19 recordsLinked to original sources

arXiv2010

Mean-field methods in evolutionary duplication-innovation-loss models for the genome-level repertoire of protein domains

We present a combined mean-field and simulation approach to different models describing the dynamics of classes formed by elements that can appear, disappear or copy themselves. These models, related to a paradigm duplication-innovation model known as Chinese Restaurant Process, are devised to reproduce the scaling behavior observed in the genome-wide repertoire of protein domains of all known species. In view of these data, we discuss the qualitative and quantitative differences of the alternative model formulations, focusing in particular on the roles of element loss and of the specificity of empirical domain classes.

q-bio.GN↗

arXiv2009

Feedback topology and XOR-dynamics in Boolean networks with varying input structure

We analyse a model of fixed in-degree Random Boolean Networks in which the fraction of input-receiving nodes is controlled by a parameter gamma. We investigate analytically and numerically the dynamics of graphs under a parallel XOR updating scheme. This scheme is interesting because it is accessible analytically and its phenomenology is at the same time under control, and as rich as the one of general Boolean networks. Biologically, it is justified on abstract grounds by the fact that all existing interactions play a dynamical role. We give analytical formulas for the dynamics on general graphs, showing that with a XOR-type evolution rule, dynamic features are direct consequences of the topological feedback structure, in analogy with the role of relevant components in Kauffman networks. Considering graphs with fixed in-degree, we characterize analytically and numerically the feedback regions using graph decimation algorithms (Leaf Removal). With varying gamma, this graph ensemble shows a phase transition that separates a tree-like graph region from one in which feedback components emerge. Networks near the transition point have feedback components made of disjoint loops, in which each node has exactly one incoming and one outgoing link. Using this fact we provide analytical estimates of the maximum period starting from topological considerations.

cond-mat.stat-mech↗

arXiv2009

Functional models for large-scale gene regulation networks: realism and fiction

High-throughput experiments are shedding light on the topology of large regulatory networks and at the same time their functional states, namely the states of activation of the nodes (for example transcript or protein levels) in different conditions, times, environments. We now possess a certain amount of information about these two levels of description, stored in libraries, databases and ontologies. A current challenge is to bridge the gap between topology and function, i.e. developing quantitative models aimed at characterizing the expression patterns of large sets of genes. However, approaches that work well for small networks become impossible to master at large scales, mainly because parameters proliferate. In this review we discuss the state of the art of large-scale functional network models, addressing the issue of what can be considered as realistic and what the main limitations may be. We also show some directions for future work, trying to set the goals that future models should try to achieve. Finally, we will emphasize the possible benefits in the understanding of biological mechanisms underlying complex multifactorial diseases, and in the development of novel strategies for the description and the treatment of such pathologies.

q-bio.MN↗

arXiv2009

A basic swimmer at low Reynolds number

Swimming and pumping at low Reynolds numbers are subject to the "Scallop theorem", which states that there will be no net fluid flow for time reversible motions. Living organisms such as bacteria and cells are subject to this constraint, and so are existing and future artificial "nano-bots" or microfluidic pumps. We study a very simple mechanism to induce fluid pumping, based on the forced motion of three colloidal beads through a cycle that breaks time-reversal symmetry. Optical tweezers are used to vary the inter-bead distance. This model is inspired by a strut-based theoretical swimmer proposed by Najafi and Golestanian [Phys.Rev. E, 69, 062901, 2004], but in this work the relative softness of the optical trapping potential introduces a new control parameter. We show that this system is able to generate flow in a controlled fashion, characterizing the model experimentally and numerically.

cond-mat.soft↗

arXiv2008

Identity and divergence of protein domain architectures after the Yeast Whole Genome Duplication event

Analyzing the properties of duplicate genes during evolution is useful to understand the development of new cell functions. The yeast S. cerevisiae is a useful testing ground for this problem, because its duplicated genes with different evolutionary birth and destiny are well distinguishable. In particular, there is a clear detection for the occurrence of a Whole Genome Duplication (WGD) event in S. cerevisiae, and the genes derived from this event (WGD paralogs) are known. We studied WGD and non-WGD duplicates by two parallel analysis based on structural protein domains and on Gene Ontology annotation scheme respectively. The results show that while a large number of ``duplicable'' structural domains is shared in local and global duplications, WGD and non-WGD paralogs tend to have different functions. The reason for this is the existence of WGD and non-WGD specific domains with largely different functions. In agreement with the recent findings of Wapinski and collaborators (Nature 449, 2007), WGD paralogs often perform ``core'' cell functions, such as translation and DNA replication, while local duplications associate with ``peripheral'' functions such as response to stress. Our results also support the fact that domain architectures are a reliable tool to detect homology, as the domains of duplicates are largely invariant with date and nature of the duplication, while their sequences and also their functions might migrate.

q-bio.GN↗

arXiv2008

Exchangeable Random Networks

We introduce and study a class of exchangeable random graph ensembles. They can be used as statistical null models for empirical networks, and as a tool for theoretical investigations. We provide general theorems that carachterize the degree distribution of the ensemble graphs, together with some features that are important for applications, such as subgraph distributions and kernel of the adjacency matrix. These results are used to compare to other models of simple and complex networks. A particular case of directed networks with power-law out--degree is studied in more detail, as an example of the flexibility of the model in applications.

math.PR↗

arXiv2008

Universal Features in the Genome-level Evolution of Protein Domains

Protein domains are found on genomes with notable statistical distributions, which bear a high degree of similarity. Previous work has shown how these distributions can be accounted for by simple models, where the main ingredients are probabilities of duplication, innovation, and loss of domains. However, no one so far has addressed the issue that these distributions follow definite trends depending on protein-coding genome size only. We present a stochastic duplication/innovation model, falling in the class of so-called Chinese Restaurant Processes, able to explain this feature of the data. Using only two universal parameters, related to a minimal number of domains and to the relative weight of innovation to duplication, the model reproduces two important aspects: (a) the populations of domain classes (the sets, related to homology classes, containing realizations of the same domain in different proteins) follow common power-laws whose cutoff is dictated by genome size, and (b) the number of domain families is universal and markedly sublinear in genome size. An important ingredient of the model is that the innovation probability decreases with genome size. We propose the possibility to interpret this as a global constraint given by the cost of expanding an increasingly complex interactome.

q-bio.GN↗

arXiv2008

A comparative evolutionary study of transcription networks

We present a comparative analysis of large-scale topological and evolutionary properties of transcription networks in three species, the two distant bacteria E. coli and B. subtilis, and the yeast S. cerevisiae. The study focuses on the global aspects of feedback and hierarchy in transcriptional regulatory pathways. While confirming that gene duplication has a significant impact on the shaping of all the analyzed transcription networks, our results point to distinct trends between the bacteria, where time constraints in the transcription of downstream genes might be important in shaping the hierarchical structure of the network, and yeast, which seems able to sustain a higher wiring complexity, that includes the more feedback, intricate hierarchy, and the combinatorial use of heterodimers made of duplicate transcription factors.

q-bio.MN↗

arXiv2007

DIA-MCIS. An Importance Sampling Network Randomizer for Network Motif Discovery and Other Topological Observables in Transcription Networks

Transcription networks, and other directed networks can be characterized by some topological observables such as for example subgraph occurrence (network motifs). In order to perform such kind of analysis, it is necessary to be able to generate suitable randomized network ensembles. Typically, one considers null networks with the same degree sequences of the original ones. The commonly used algorithms sometimes have long convergence times, and sampling problems. We present here an alternative, based on a variant of the importance sampling Montecarlo developed by Chen et al. [1].

q-bio.QM↗

arXiv2007

Random Networks Tossing Biased Coins

In statistical mechanical investigations on complex networks, it is useful to employ random graphs ensembles as null models, to compare with experimental realizations. Motivated by transcription networks, we present here a simple way to generate an ensemble of random directed graphs with, asymptotically, scale-free outdegree and compact indegree. Entries in each row of the adjacency matrix are set to be zero or one according to the toss of a biased coin, with a chosen probability distribution for the biases. This defines a quick and simple algorithm, which yields good results already for graphs of size n ~ 100. Perhaps more importantly, many of the relevant observables are accessible analytically, improving upon previous estimates for similar graphs.

cond-mat.stat-mech↗

arXiv2007

Hierarchy and Feedback in the Evolution of the E. coli Transcription Network

The E.coli transcription network has an essentially feedforward structure, with, however, abundant feedback at the level of self-regulations. Here, we investigate how these properties emerged during evolution. An assessment of the role of gene duplication based on protein domain architecture shows that (i) transcriptional autoregulators have mostly arisen through duplication, while (ii) the expected feedback loops stemming from their initial cross-regulation are strongly selected against. This requires a divergent coevolution of the transcription factor DNA-binding sites and their respective DNA cis-regulatory regions. Moreover, we find that the network tends to grow by expansion of the existing hierarchical layers of computation, rather than by addition of new layers. We also argue that rewiring of regulatory links due to mutation/selection of novel transcription factor/DNA binding interactions appears not to significantly affect the network global hierarchy, and that horizontally transferred genes are mainly added at the bottom, as new target nodes. These findings highlight the important evolutionary roles of both duplication and selective deletion of crosstalks between autoregulators in the emergence of the hierarchical transcription network of E.coli.

q-bio.MN↗

arXiv2006

Fluctuations of a driven membrane in an electrolyte

We develop a model for a driven cell- or artificial membrane in an electrolyte. The system is kept far from equilibrium by the application of a DC electric field or by concentration gradients, which causes ions to flow through specific ion-conducting units (representing pumps, channels or natural pores). We consider the case of planar geometry and Debye-Hückel regime, and obtain the membrane equation of motion within Stokes hydrodynamics. At steady state, the applied field causes an accumulation of charges close to the membrane, which, similarly to the equilibrium case, can be described with renormalized membrane tension and bending modulus. However, as opposed to the equilibrium situation, we find new terms in the membrane equation of motion, which arise specifically in the out-of-equilibrium case. We show that these terms lead in certain conditions to instabilities.

cond-mat.soft↗

arXiv2006

Randomization and Feedback Properties of Directed Graphs Inspired by Gene Networks

Having in mind the large-scale analysis of gene regulatory networks, we review a graph decimation algorithm, called "leaf-removal", which can be used to evaluate the feedback in a random graph ensemble. In doing this, we consider the possibility of analyzing networks where the diagonal of the adjacency matrix is structured, that is, has a fixed number of nonzero entries. We test these ideas on a network model with fixed degree, using both numerical and analytical calculations. Our results are the following. First, the leaf-removal behavior for large system size enables to distinguish between different regimes of feedback. We show their relations and the connection with the onset of complexity in the graph. Second, the influence of the diagonal structure on this behavior can be relevant.

q-bio.MN↗

arXiv2005

The Logic Backbone of a Transcription Network

A great part of the effort in the study of coarse grained models of transcription networks is directed to the analysis of their dynamical features. In this letter, we consider the \emph{equilibrium} properties of such systems, showing that the logic backbone underlying all dynamic descriptions has the structure of a computational optimization problem. It involves variables, which correspond to gene expression levels, and constraints, which describe the effect of \emph{cis-}regulatory signal integration functions. In the simple paradigmatic case of Boolean variables and signal integration functions, we derive and discuss phase diagrams. Notably, the model exhibits a connectivity transition between a regime of simple, but uncertain, gene control, to a regime of complex combinatorial control.

q-bio.MN↗

arXiv2005

Hydrodynamic induced deformation and orientation of a microscopic elastic filament

We describe simulations of a microscopic elastic filament immersed in a fluid and subject to a uniform external force. Our method accounts for the hydrodynamic coupling between the flow generated by the filament and the friction force it experiences. While models that neglect this coupling predict a drift in a straight configuration, our findings are very different. Notably, a force with a component perpendicular to the filament axis induces bending and perpendicular alignment. Moreover, with increasing force we observe four shape regimes, ranging from slight distortion to a state of tumbling motion that lacks a steady state. We also identify the appearance of marginally stable structures. Both the instability of these shapes and the observed alignment can be explained by the combined action of induced bending and non-local hydrodynamic interactions. Most of these effects should be experimentally relevant for stiff micro-filaments, such as microtubules.

cond-mat.soft↗

arXiv2005

The large-scale logico-chemical structure of a transcriptional regulation network

Identity, response to external stimuli, and spatial architecture of a living system are central topics of molecular biology. Presently, they are largely seen as a result of the interplay between a gene repertoire and the regulatory machinery of the cell. At the transcriptional level, the cis-regulatory regions establish sets of interdependencies between transcription factors and genes, including other transcription factors. These ``transcription networks'' are too large to be approached globally with a detailed dynamical model. In this paper, we describe an approach to this problem that focuses solely on the compatibility between gene expression patterns and signal integration functions, discussing calculations carried on the simplest, Boolean, realization of the model, and a first application to experimental data sets.

q-bio.MN↗

arXiv2003

Metachronal wave and hydrodynamic interaction for deterministic switching rowers

We employ a model system, called rowers, as a generic physical framework to define the problem of the coordinated motion of cilia (the metachronal wave) as a far from equilibrium process. Rowers are active (two-state) oscillators interacting solely through forces of hydrodynamic origin. In this work, we consider the case of fully deterministic dynamics, find analytical solutions of the equation of motion in the long wavelength (continuum) limit, and investigate numerically the short wavelength limit. We prove the existence of metachronal waves below a characteristic wavelength. Such waves are unstable and become stable only if the sign of the coupling is reversed. We also find that with normal hydrodynamic interaction the metachronal pattern has the form of stable trains of traveling wave packets sustained by the onset of anti-coordinated beating of consecutive rowers.

physics.bio-ph↗

arXiv2002

A simulation study of the dynamics of a driven filament in an Aristotelian fluid

We describe a method, based on techniques used in molecular dynamics, for simulating the inertialess dynamics of an elastic filament immersed in a fluid. The model is used to study the "one-armed swimmer". That is, a flexible appendage externally perturbed at one extremity. For small amplitude motion our simulations confirm theoretical predictions that, for a filament of given length and stiffness, there is a driving frequency that is optimal for both speed and efficiency. However, we find that to calculate absolute values of the swimming speed we need to slightly modify existing theoretical approaches. For the more realistic case of large amplitude motion we find that while the basic picture remains the same, the dependence of the swimming speed on both frequency and amplitude is substantially modified. For realistic amplitudes we show that the one armed swimmer is comparatively neither inefficient nor slow. This begs the question, why are there little or no one armed swimmers in nature?

physics.bio-ph↗