arXiv subjects

Pedro T. Monteiro

Publications and source records attributed to Pedro T. Monteiro.

9 recordsLinked to original sources

arXiv2026

pyModRev: a Python Tool for Model Revision of Boolean Networks

Biological regulatory networks can be represented by computational models, which allow the study and analysis of biological behaviours, therefore providing a better understanding of a given biological process. However, as new information is acquired, biological models may need to be revised in order to also account for this new information. Current model revision tools are scarce and often lack the flexibility to integrate with broader analysis workflows. Here, we present pyModRev, an enhanced iteration of the model revision tool ModRev, capable of verifying the consistency of Boolean regulatory models, and finding minimal repairs in case of inconsistency. pyModRev supports model validation against both steady state observations as well as time-series data, being able to consider different update schemes simultaneously. pyModRev supports different model formats, and is available as a Python package in PyPI, for easy integration with other model analysis tools, significantly improving accessibility and utility for the logical modelling community.

cs.CE↗

arXiv2026

Optimizing Donor Outreach for Blood Collection Sessions: A Scalable Decision Support Framework

Blood donation centers face challenges in matching supply with demand while managing donor availability. Although targeted outreach is important, it can cause donor fatigue via over-solicitation. Effective recruitment requires targeting the right donors at the right time, balancing constraints with donor convenience and eligibility. Despite extensive work on blood supply chain optimization and growing interest in algorithmic donor recruitment, the operational problem of assigning donors to sessions across a multi-site network, taking into account eligibility, capacity, blood-type demand targets, geographic convenience, and donor safety, remains unaddressed. We address this gap with an optimization framework for donor invitation scheduling incorporating donor eligibility, travel convenience, blood-type demand targets, and penalties. We evaluate two strategies: (i) a binary integer linear programming (BILP) formulation and (ii) an efficient greedy heuristic. Evaluation uses the registry from Instituto Português do Sangue e da Transplantação (IPST) for invite planning in the Lisbon operational region using 4-month windows. A prospective pipeline integrates organic attendance forecasting, quantile-based demand targets, and residual capacity estimation for forward-looking invitation plans. Results reveal its key role in closing the supply-demand gap in the Lisbon operational region. A controlled comparison shows that the greedy heuristic achieves results comparable to the BILP, with 188x less peak memory and 115x faster runtime; trade-offs include 3.9 pp lower demand fulfillment (86.1% vs. 90.0%), larger donor-session distance, higher adverse-reaction donor exposure, and greater invitation burden per non-high-frequency donor, reflecting local versus global optimization. Experiments assess how constraint-aware scheduling can close gaps by mobilizing eligible inactive/lapsing donors.

cs.AI↗

arXiv2025

Computation of Immediate Neighbours of Monotone Boolean Functions

Boolean networks constitute relevant mathematical models to study the behaviours of genetic and signalling networks. These networks define regulatory influences between molecular nodes, each being associated to a Boolean variable and a regulatory (local) function specifying its dynamical behaviour depending on its regulators. However, existing data is mostly insufficient to adequately parametrise a model, that is to uniquely define a regulatory function for each node. With the intend to support model parametrisation, this paper presents results on the set of Boolean functions compatible with a given regulatory structure, i.e. the partially ordered set of monotone non-degenerate Boolean functions. More precisely, we present original rules to obtain the direct neighbours of any function of this set. Besides a theoretical interest, presented results will enable the development of more efficient methods for Boolean network synthesis and revision, benefiting from the progressive exploration of the vicinity of regulatory functions.

cs.DM↗

arXiv2021

Boolean function metrics can assist modelers to check and choose logical rules

Computational models of biological processes provide one of the most powerful methods for a detailed analysis of the mechanisms that drive the behavior of complex systems. Logic-based modeling has enhanced our understanding and interpretation of those systems. Defining rules that determine how the output activity of biological entities is regulated by their respective inputs has proven to be challenging, due to increasingly larger models and the presence of noise in data, allowing multiple model parameterizations to fit the experimental observations. We present several Boolean function metrics that provide modelers with the appropriate framework to analyze the impact of a particular model parameterization. We demonstrate the link between a semantic characterization of a Boolean function and its consistency with the model's underlying regulatory structure. We further define the properties that outline such consistency and show that several of the Boolean functions under study violate them, questioning their biological plausibility and subsequent use. We also illustrate that regulatory functions can have major differences with regard to their asymptotic output behavior, with some of them being biased towards specific Boolean outcomes when others are dependent on the ratio between activating and inhibitory regulators. Application results show that in a specific signaling cancer network, the function bias can be used to guide the choice of logical operators for a model that matches data observations. Moreover, graph analysis indicates that the standardized Boolean function bias becomes more prominent with increasing numbers of regulators, confirming the fact that rule specification can effectively determine regulatory outcome despite the complex dynamics of biological networks.

q-bio.MN↗

arXiv2019

Partial Order on the set of Boolean Regulatory Functions

Logical models have been successfully used to describe regulatory and signaling networks without requiring quantitative data. However, existing data is insufficient to adequately define a unique model, rendering the parametrization of a given model a difficult task. Here, we focus on the characterization of the set of Boolean functions compatible with a given regulatory structure, i.e. the set of all monotone nondegenerate Boolean functions. We then propose an original set of rules to locally explore the direct neighboring functions of any function in this set, without explicitly generating the whole set. Also, we provide relationships between the regulatory functions and their corresponding dynamics. Finally, we illustrate the usefulness of this approach by revisiting Probabilistic Boolean Networks with the model of T helper cell differentiation from Mendoza & Xenarios.

cs.DM↗

arXiv2014

Quantification of reachable attractors in asynchronous discrete dynamics

Motivation: Models of discrete concurrent systems often lead to huge and complex state transition graphs that represent their dynamics. This makes difficult to analyse dynamical properties. In particular, for logical models of biological regulatory networks, it is of real interest to study attractors and their reachability from specific initial conditions, i.e. to assess the potential asymptotical behaviours of the system. Beyond the identification of the reachable attractors, we propose to quantify this reachability. Results: Relying on the structure of the state transition graph, we estimate the probability of each attractor reachable from a given initial condition or from a portion of the state space. First, we present a quasi-exact solution with an original algorithm called Firefront, based on the exhaustive exploration of the reachable state space. Then, we introduce an adapted version of Monte Carlo simulation algorithm, termed Avatar, better suited to larger models. Firefront and Avatar methods are validated and compared to other related approaches, using as test cases logical models of synthetic and biological networks. Availability: Both algorithms are implemented as Perl scripts that can be freely downloaded from http://compbio.igc.gulbenkian.pt/nmd/node/59 along with Supplementary Material.

cs.DM↗

arXiv2013

SBML Qualitative Models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools

Background: Qualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing. Results: We present the System Biology Markup Language (SBML) Qualitative Models Package ("qual"), an extension of the SBML Level 3 standard designed for computer representation of qualitative models of biological networks. We demonstrate the interoperability of models via SBML qual through the analysis of a specific signalling network by three independent software tools. Furthermore, the cooperative development of the SBML qual format paved the way for the development of LogicalModel, an open-source model library, which will facilitate the adoption of the format as well as the collaborative development of algorithms to analyze qualitative models. Conclusion: SBML qual allows the exchange of qualitative models among a number of complementary software tools. SBML qual has the potential to promote collaborative work on the development of novel computational approaches, as well as on the specification and the analysis of comprehensive qualitative models of regulatory and signalling networks.

q-bio.MN↗

arXiv2010

Efficient parameter search for qualitative models of regulatory networks using symbolic model checking

Investigating the relation between the structure and behavior of complex biological networks often involves posing the following two questions: Is a hypothesized structure of a regulatory network consistent with the observed behavior? And can a proposed structure generate a desired behavior? Answering these questions presupposes that we are able to test the compatibility of network structure and behavior. We cast these questions into a parameter search problem for qualitative models of regulatory networks, in particular piecewise-affine differential equation models. We develop a method based on symbolic model checking that avoids enumerating all possible parametrizations, and show that this method performs well on real biological problems, using the IRMA synthetic network and benchmark experimental data sets. We test the consistency between the IRMA network structure and the time-series data, and search for parameter modifications that would improve the robustness of the external control of the system behavior.

q-bio.QM↗

arXiv2008

Temporal Logic Patterns for Querying Dynamic Models of Cellular Interaction Networks

Models of the dynamics of cellular interaction networks have become increasingly larger in recent years. Formal verification based on model checking provides a powerful technology to keep up with this increase in scale and complexity. The application of model-checking approaches is hampered, however, by the difficulty for non-expert users to formulate appropriate questions in temporal logic. In order to deal with this problem, we propose the use of patterns, that is, high-level query templates that capture recurring biological questions and that can be automatically translated into temporal logic. The applicability of the developed set of patterns has been investigated by the analysis of an extended model of the network of global regulators controlling the carbon starvation response in Escherichia coli.

q-bio.QM↗