arXiv subjects

Ludvig Lizana

Publications and source records attributed to Ludvig Lizana.

At least 19 recordsLinked to original sources

arXiv2026

Multifractal Scaling in Hi-C Maps

The three-dimensional organization of the genome exhibits rich, scale-dependent structure, as revealed by both chromosome contact maps (e.g., Hi-C maps) and chromatin density measured by microscopy. Recent studies have reported multifractal scaling in these data. Yet, the origin of this scaling behavior remains unclear: existing efforts describe it through postulated models. Here, we show that the multifractal structure of Hi-C maps is a direct consequence of the power-law contact probability $P(s)$, which is itself an empirical observable measured from Hi-C maps. Starting from $P(s)$ with a single exponent $\gamma$, we analytically derive the mass exponent $\tau(q)$, which characterizes how the $q$-th moment of contact density scales with box size $l$ used to coarse-grain the genomic coordinate. This multifractal behavior reflects the geometric competition between intra- and inter-segment contacts. We find that the slope of $\tau(q)$ at large $q$ is given by $2 -\gamma$ when $\gamma <1$, and by $1$ when $\gamma \geq 1$. We further show that this behavior is robust to noise and consistent across diverse organisms, indicating that it is a universal feature of chromatin organization. We extend our analysis into double-exponent $P(s)$, and show the $l$ dependence in multifractal behavior. Taken together, these results provide a physical explanation for multifractal scaling and establish a direct link between the multifractality in Hi-C maps and polymer contact statistics, with the large-$q$ slope of $\tau(q)$ mapping onto a known polymer contact exponent.

cond-mat.stat-mech↗

arXiv2026

Beyond average: heterogeneous first-passage dynamics in many-particle systems with resetting

We study how stochastic resetting affects first-passage processes in systems of many interacting particles. While resetting is well understood for single-particle dynamics, its consequences for collective behavior remain less clear. We consider a protocol in which all surviving particles are reset to the position of the most extreme one, motivated by problems in artificial selection and avoidance. Using stochastic simulations of particles diffusing in a confining potential with an absorbing boundary, we examine two notions of arrival: when the first particle reaches the boundary and the point at which half of the particles do. We find that resetting produces broad distributions of arrival times with heavy tails and extended plateaus that span several orders of magnitude. As the resetting rate increases, the mean arrival time grows and diverges beyond a threshold. Trajectory-level analysis also reveals strong heterogeneity, with very short and very long absorption times. These results show that collective resetting lacks a single characteristic time scale and that the definition of arrival is crucial for understanding and controlling such systems.

cond-mat.stat-mech↗

arXiv2024

General Theory for Group Resetting with Application to Avoidance

We present a general theoretical framework for group resetting dynamics in a potential landscape. While traditional resetting models typically focus on a single particle, we consider a group of particles whose collective dynamics govern the resetting. We extend existing resetting theories to cover extreme-value group resetting. This has applications from bacterial evolution under antibiotic pressure to swarm-search optimization. Using renewal theory, we derive a Fokker-Planck equation for the spatial distribution of the group's center of mass, treated as an effective particle. This formalism yields analytical expressions for key observables such as the stationary mean position and variance. We also study a group avoidance problem, where the particles must avoid an undesirable region. Such problems have recently been studied in contexts such as preventing critically high water levels in dams and controlling excessive financial leverage. Our framework offers new insight into how resetting can optimize group-level search and avoidance strategies.

cond-mat.stat-mech↗

arXiv2024

Target search on networks-within-networks with applications to protein-DNA interactions

We present a novel framework for understanding node target search in systems organized as hierarchical networks-within-networks. Our work generalizes traditional search models on complex networks, where the mean-first passage time is typically inversely proportional to the node degree. However, real-world search processes often span multiple network layers, such as moving from an external environment into a local network, and then navigating several internal states. This multilayered complexity appears in scenarios such as international travel networks, tracking email spammers, and the dynamics of protein-DNA interactions in cells. Our theory addresses these complex systems by modeling them as a three-layer multiplex network: an external source layer, an intermediate spatial layer, and an internal state layer. We derive general closed-form solutions for the steady-state flux through a target node, which serves as a proxy for inverse mean-first passage time. Our results reveal a universal relationship between search efficiency and network-specific parameters. This work extends the current understanding of multiplex networks by focusing on systems with hierarchically connected layers. Our findings have broad implications for fields ranging from epidemiology to cellular biology and provide a more comprehensive understanding of search dynamics in complex, multilayered environments.

physics.bio-ph↗

arXiv2024

Identifying stable communities in Hi-C data using a multifractal null model

Chromosome capture techniques like Hi-C have expanded our understanding of mammalian genome 3D architecture and how it influences gene activity. To analyze Hi-C data sets, researchers increasingly treat them as DNA-contact networks and use standard community detection techniques to identify mesoscale 3D communities. However, there are considerable challenges in finding significant communities because the Hi-C networks have cross-scale interactions and are almost fully connected. This paper presents a pipeline to distil 3D communities that remain intact under experimental noise. To this end, we bootstrap an ensemble of Hi-C datasets representing noisy data and extract 3D communities that we compare with the unperturbed dataset. Notably, we extract the communities by maximizing local modularity (using the Generalized Louvain method), which considers the multifractal spectrum recently discovered in Hi-C maps. Our pipeline finds that stable communities (under noise) typically have above-average internal contact frequencies and tend to be enriched in active chromatin marks. We also find they fold into more nested cross-scale hierarchies than less stable ones. Apart from presenting how to systematically extract robust communities in Hi-C data, our paper offers new ways to generate null models that take advantage of the network's multifractal properties. We anticipate this has a broad applicability to several network applications.

physics.bio-ph↗

arXiv2024

A general mechanism for enhancer-insulator pairing reveals heterogeneous dynamics in long-distant 3D gene regulation

Cells regulate fates and complex body plans using spatiotemporal signaling cascades that alter gene expression. Enhancers, short DNA sequences (50-150 base pairs), help coordinate these cascades by attracting regulatory proteins to enhance the transcription of distal genes by binding to promoters. In humans, there are hundreds of thousands of enhancers dispersed across the genome, which poses a challenging coordination task to prevent unintended gene activation. To mitigate this problem, the genome contains additional DNA elements, insulators, that block enhancer-promoter interactions. However, there is an open problem with how the insulation works, especially as enhancer-insulator pairs may be separated by millions of base pairs. Based on recent empirical data from Hi-C experiments, this paper proposes a new mechanism that challenges the common paradigm that rests on specific insulator-insulator interactions. Instead, this paper introduces a stochastic looping model where enhancers bind weakly to surrounding chromatin. After calibrating the model to experimental data, we use simulations to study the broad distribution of hitting times between an enhancer and a promoter when there are blocking insulators. In some cases, there is a large difference between average and most probable hitting times, making it difficult to assign a typical time scale, hinting at highly defocused regulation times. We also map our computational model onto a resetting problem that allows us to derive several analytical results. Besides offering new insights into enhancer-insulator interactions, our paper advances the understanding of gene regulatory networks and causal connections between genome folding and gene activation.

q-bio.MN↗

arXiv2023

Exploring the benefits of DNA-target search with antenna

The most common gene regulation mechanism is when a protein binds to a regulatory sequence to change RNA transcription. However, these sequences are short relative to the genome length, so finding them poses a challenging search problem. This paper presents two mathematical frameworks capturing different aspects of this problem. First, we study the interplay between diffusional flux through a target where the searching proteins get sequestered on DNA far from the target because of non-specific interactions. From this model, we derive a simple formula for the optimal protein-DNA unbinding rate, maximizing the particle flux. Second, we study how the flux flows through a target on a single antenna with variable length. Here, we identify a non-trivial logarithmic correction to the linear behavior relative to the target size proposed by Smoluchowski's flux formula.

cond-mat.stat-mech↗

arXiv2023

Exploring 3D community inconsistency in human chromosome contact networks

Researchers developed chromosome capture methods such as Hi-C to better understand DNA's 3D folding in nuclei. The Hi-C method captures contact frequencies between DNA segment pairs across the genome. When analyzing Hi-C data sets, it is common to group these pairs using standard bioinformatics methods (e.g., PCA). Other approaches handle Hi-C data as weighted networks, where connected node represent DNA segments in 3D proximity. In this representation, one can leverage community detection techniques developed in complex network theory to group nodes into mesoscale communities containing similar connection patterns. While there are several successful attempts to analyze Hi-C data in this way, it is common to report and study the most typical community structure. But in reality, there are often several valid candidates. Therefore, depending on algorithm design, different community detection methods focusing on slightly different connectivity features may have differing views on the ideal node groupings. In fact, even the same community detection method may yield different results if using a stochastic algorithm. This ambiguity is fundamental to community detection and shared by most complex networks whenever interactions span all scales in the network. This is known as community inconsistency. This paper explores this inconsistency of 3D communities in Hi-C data for all human chromosomes. We base our analysis on two inconsistency metrics, one local and one global, and quantify the network scales where the community separation is most variable. For example, we find that TADs are less reliable than A/B compartments and that nodes with highly variable node-community memberships are associated with open chromatin. Overall, our study provides a helpful framework for data-driven researchers and increases awareness of some inherent challenges when clustering Hi-C data into 3D communities.

physics.soc-ph↗

arXiv2022

Mapping robust multiscale communities in chromosome contact networks

To better understand DNA's 3D folding in cell nuclei, researchers developed chromosome capture methods such as Hi-C that measure the contact frequencies between all DNA segment pairs across the genome. As Hi-C data sets often are massive, it is common to use bioinformatics methods to group DNA segments into 3D regions with correlated contact patterns, such as Topologically Associated Domains (TADs) and A/B compartments. Recently, another research direction emerged that treats the Hi-C data as a network of 3D contacts. In this representation, one can use community detection algorithms from complex network theory that group nodes into tightly connected mesoscale communities. However, because Hi-C networks are so densely connected, several node partitions may represent feasible solutions to the community detection problem but are indistinguishable unless including other data. Because this limitation is a fundamental property of the network, this problem persists regardless of the community-finding or data-clustering method. To help remedy this problem, we developed a method that charts the solution landscape of network partitions in Hi-C data from human cells. Our approach allows us to scan seamlessly through the scales of the network and determine regimes where we can expect reliable community structures. We find that some scales are more robust than others and that strong clusters may differ significantly. Our work highlights that finding a robust community structure hinges on thoughtful algorithm design or method cross-evaluation.

physics.bio-ph↗

arXiv2022

Modelling chromosome-wide target search

The most common gene regulation mechanism is when a transcription factor protein binds to a regulatory sequence to increase or decrease RNA transcription. However, transcription factors face two main challenges when searching for these sequences. First, they are vanishingly short relative to the genome length. Second, many nearly identical sequences are scattered across the genome, causing proteins to suspend the search. But as pointed out in a computational study of LacI regulation in Escherichia coli, such almost-targets may lower search times if considering DNA looping. In this paper, we explore if this also occurs over chromosome-wide distances. To this end, we developed a cross-scale computational framework that combines established facilitated-diffusion models for basepair-level search and a network model capturing chromosome-wide leaps. To make our model realistic, we used Hi-C data sets as a proxy for 3D proximity between long-ranged DNA segments and binding profiles for more than 100 transcription factors. Using our cross-scale model, we found that median search times to individual targets critically depend on a network metric combining node strength (sum of link weights) and local dissociation rates. Also, by randomizing these rates, we found that some actual 3D target configurations stand out as considerably faster or slower than their random counterparts. This finding hints that chromosomes' 3D structure funnels essential transcription factors to relevant DNA regions.

q-bio.QM↗

arXiv2021

Fractal and knot-free chromosomes facilitate nucleoplasmic transport

Chromosomes in the nucleus assemble into hierarchies of 3D domains that, during interphase, share essential features with a knot-free condensed polymer known as the fractal globule (FG). The FG-like chromosome likely affects macromolecular transport, yet its characteristics remain poorly understood. Using computer simulations and scaling analysis, we show that the 3D folding and macromolecular size of the chromosomes determine their transport characteristics. Large-scale subdiffusion occurs at a critical particle size where the network of accessible volumes is critically connected. Condensed chromosomes have connectivity networks akin to simple Bernoulli bond percolation clusters, regardless of the polymer models. However, even if the network structures are similar, the tracer's walk dimension varies. It turns out that the walk dimension depends on the network topology of the accessible volume and dynamic heterogeneity of the tracer's hopping rate. We find that the FG structure has a smaller walk dimension than other random geometries, suggesting that the FG-like chromosome structure accelerates macromolecular diffusion and target-search.

physics.bio-ph↗

arXiv2018

Genomic 3D-compartments emerge from unfolding mitotic chromosomes

The 3D organisation of the genome in interphase cells is not a randomly folded polymer. Rather, experiments show that chromosomes arrange into a network of 3D compartments that correlate with biological processes, such as transcription, chromatin modifications, and protein binding. However, these compartments do not exist during cell division when the DNA is condensed, and it is unclear how and when they emerge. In this paper, we focus on the early stages after cell-division as the chromosomes start to decondense. We use a simple polymer model to understand the types of 3D structures that emerge from local unfolding of a compact initial state. From simulations, we recover 3D compartments, such as TADs and A/B compartments, that are consistently detected in Chromosome Capture Experiments across cell types and organisms. This suggests that the large-scale 3D organisation is a result of an inflation process.

physics.bio-ph↗

arXiv2018

Mapping the spectrum of 3D communities in human chromosome conformation capture data

Several experiments show that the three dimensional (3D) organization of chromosomes affects genetic processes such as transcription and gene regulation. To better understand this connection, researchers developed the Hi-C method that is able to detect the pairwise physical contacts of all chromosomal loci. The Hi-C data show that chromosomes are composed of 3D compartments that range over a variety of scales. However, it is challenging to systematically detect these cross-scale structures. Most studies have therefore designed methods for specific scales to study foremost topologically associated domains (TADs) and A/B compartments. To go beyond this limitation, we tailor a network community detection method that finds communities in compact fractal globule polymer systems. Our method allows us to continuously scan through all scales with a single resolution parameter. We found: (i) polymer segments belonging to the same 3D community do not have to be in consecutive order along the polymer chain. In other words, several TADs may belong to the same 3D community. (ii) CTCF proteins---a loop-stabilizing protein that is ascribed a big role in TAD formation---are well correlated with community borders only at one level of organization. (iii) TADs and A/B compartments are traditionally treated as two weakly related 3D structures and detected with different algorithms. With our method, we detect both by simply adjusting the resolution parameter. We therefore argue that they represent two specific levels of a continuous spectrum 3D communities, rather than seeing them as different structural entities.

q-bio.GN↗

arXiv2018

Persistence of Non-Markovian Gaussian Stationary Processes in Discrete Time

The persistence of a stochastic variable is the probability that it does not cross a given level during a fixed time interval. Although persistence is a simple concept to understand, it is in general hard to calculate. Here we consider zero mean Gaussian stationary processes in discrete time $n$. Few results are known for the persistence $P_0(n)$ in discrete time, except the large time behavior which is characterized by the nontrivial constant $\theta$ through $P_0(n)\sim \theta^n$. Using a modified version of the Independent Interval Approximation (IIA) that we developed before, we are able to calculate $P_0(n)$ analytically in $z$-transform space in terms of the autocorrelation function $A(n)$. If $A(n)\to0$ as $n\to\infty$, we extract $\theta$ numerically, while if $A(n)=0$, for finite $n>N$, we find $\theta$ exactly (within the IIA). We apply our results to three special cases: the nearest neighbor-correlated "first order moving average process" where $A(n)=0$ for $ n>1$, the double exponential-correlated "second order autoregressive process" where $A(n)=c_1\lambda_1^n+c_2\lambda_2^n$, and power law-correlated variables where $A(n)\sim n^{-\mu}$. Apart from the power-law case when $\mu<5$, we find excellent agreement with simulations.

cond-mat.stat-mech↗

arXiv2017

Zero-Crossing Statistics for Non-Markovian Time Series

In applications spaning from image analysis and speech recognition, to energy dissipation in turbulence and time-to failure of fatigued materials, researchers and engineers want to calculate how often a stochastic observable crosses a specific level, such as zero. At first glance this problem looks simple, but it is in fact theoretically very challenging. And therefore, few exact results exist. One exception is the celebrated Rice formula that gives the mean number of zero-crossings in a fixed time interval of a zero-mean Gaussian stationary processes. In this study we use the so-called Independent Interval Approximation to go beyond Rice's result and derive analytic expressions for all higher-order zero-crossing cumulants and moments. Our results agrees well with simulations for the non-Markovian autoregressive model.

cond-mat.stat-mech↗

arXiv2016

Tracer Particles in Two-Dimensional Elastic Networks Diffuse Logarithmically Slow

Several experiments on tagged molecules or particles in living systems suggest that they move anomalously slow - their mean squared displacement (MSD) increase slower than linearly with time. Leading models aimed at understanding these experiments predict that the MSD grows as a power law with a growth exponent that is smaller than unity. However, in some experiments the exponent is so small $(\sim 0.1-0.2)$ that they hint towards other mechanisms at play. In this paper, we theoretically demonstrate how in-plane collective modes excited by thermal fluctuations in a two dimensional membrane lead to logarithmic time dependence for the mean square displacement of a tracer particle.

cond-mat.stat-mech↗

arXiv2016

A simple method to calculate first-passage time densities of non-smooth processes

Numerous applications all the way from biology and physics to economics depend on the density of first crossings over a boundary. Motivated by the lack of analytical tools for computing first-passage time densities (FPTDs) for complex problems, we propose a new simple method based on the Independent Interval Approximation (IIA). We generalise previous formulations of the IIA to handle non-smooth processes, and derive a closed form expression for the FPTD in Laplace and $z$-transform space for arbitrary boundary and starting points in one dimension. We focus on Markov processes for which the IIA is exact. To apply our equations, we calculate the FPTD in two cases: the Ornstein-Uhlenbeck process and the discrete time Brownian walk. Our results are in good agreement with Langevin dynamics simulations.

cond-mat.stat-mech↗

arXiv2015

Many-body effects in tracer particle diffusion with applications for single-protein dynamics on DNA

30% of the DNA in E. coli bacteria is covered by proteins. Such high degree of crowding affect the dynamics of generic biological processes (e.g. gene regulation, DNA repair, protein diffusion etc.) in ways that are not yet fully understood. In this paper, we theoretically address the diffusion constant of a tracer particle in a one dimensional system surrounded by impenetrable crowder particles. While the tracer particle always stays on the lattice, crowder particles may unbind to a surrounding bulk and rebind at another or the same location. In this scenario we determine how the long time diffusion constant ${\cal D}$ (after many unbinding events) depends on (i) the unbinding rate of crowder particles $k_{\rm off}$, and (ii) crowder particle line density $ρ$, from simulations (Gillespie algorithm) and analytical calculations. For small $k_{\rm off}$, we find ${\cal D}\sim k_{\rm off}/ρ^2$ when crowder particles are immobile on the line, and ${\cal D}\sim \sqrt{D k_{\rm off}}/ρ$ when they are diffusing; $D$ is the free particle diffusion constant. For large $k_{\rm off}$, we find agreement with mean-field results which do not depend on $k_{\rm off}$. From literature values of $k_{\rm off}$ and $D$, we show that the small $k_{\rm off}$-limit is relevant for in vivo protein diffusion on a crowded DNA. Our results applies to single-molecule tracking experiments.

cond-mat.stat-mech↗