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Discriminating between rival biochemical network models : Three approaches to optimal experiment design
(2010-04-01) Mélykúti, Bence; August, Elias; Papachristodoulou, Antonis; El-Samad, Hana; Department of Engineering
Background: The success of molecular systems biology hinges on the ability to use computational models to design predictive experiments, and ultimately unravel underlying biological mechanisms. A problem commonly encountered in the computational modelling of biological networks is that alternative, structurally different models of similar complexity fit a set of experimental data equally well. In this case, more than one molecular mechanism can explain available data. In order to rule out the incorrect mechanisms, one needs to invalidate incorrect models. At this point, new experiments maximizing the difference between the measured values of alternative models should be proposed and conducted. Such experiments should be optimally designed to produce data that are most likely to invalidate incorrect model structures.Results: In this paper we develop methodologies for the optimal design of experiments with the aim of discriminating between different mathematical models of the same biological system. The first approach determines the 'best' initial condition that maximizes the L2 (energy) distance between the outputs of the rival models. In the second approach, we maximize the L2-distance of the outputs by designing the optimal external stimulus (input) profile of unit L2-norm. Our third method uses optimized structural changes (corresponding, for example, to parameter value changes reflecting gene knock-outs) to achieve the same goal. The numerical implementation of each method is considered in an example, signal processing in starving Dictyostelium amœbæ.Conclusions: Model-based design of experiments improves both the reliability and the efficiency of biochemical network model discrimination. This opens the way to model invalidation, which can be used to perfect our understanding of biochemical networks. Our general problem formulation together with the three proposed experiment design methods give the practitioner new tools for a systems biology approach to experiment design.
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Efficient, sparse biological network determination
(2009-02-23) August, Elias; Papachristodoulou, Antonis; Department of Engineering
Background: Determining the interaction topology of biological systems is a topic that currently attracts significant research interest. Typical models for such systems take the form of differential equations that involve polynomial and rational functions. Such nonlinear models make the problem of determining the connectivity of biochemical networks from time-series experimental data much harder. The use of linear dynamics and linearization techniques that have been proposed in the past can circumvent this, but the general problem of developing efficient algorithms for models that provide more accurate system descriptions remains open. Results: We present a network determination algorithm that can treat model descriptions with polynomial and rational functions and which does not make use of linearization. For this purpose, we make use of the observation that biochemical networks are in general 'sparse' and minimize the 1-norm of the decision variables (sum of weighted network connections) while constraints keep the error between data and the network dynamics small. The emphasis of our methodology is on determining the interconnection topology rather than the specific reaction constants and it takes into account the necessary properties that a chemical reaction network should have - something that techniques based on linearization can not. The problem can be formulated as a Linear Program, a convex optimization problem, for which efficient algorithms are available that can treat large data sets efficiently and uncertainties in data or model parameters. Conclusion: The presented methodology is able to predict with accuracy and efficiency the connectivity structure of a chemical reaction network with mass action kinetics and of a gene regulatory network from simulation data even if the dynamics of these systems are non-polynomial (rational) and uncertainties in the data are taken into account. It also produces a network structure that can explain the real experimental data of L. lactis and is similar to the one found in the literature. Numerical methods based on Linear Programming can therefore help determine efficiently the network structure of biological systems from large data sets. The overall objective of this work is to provide methods to increase our understanding of complex biochemical systems, particularly through their interconnection and their non-equilibrium behavior.
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Predictability of cortico-cortical connections in the mammalian brain
(2024) Molnár, F.; Horvát, S.; Gomes, A.R.R.; Armas, J.M.; Molnár, B.; Ercsey-Ravasz, M.; Knoblauch, K.; Kennedy, H.; Toroczkai, Z.; Department of Computer Science
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Mining Association Rules From a Multimodal Dataset of a Digital Therapeutics Application for Sleep Improvement Through a Healthy Lifestyle : Quantitative Study
(2026) Biedebach, Luka; Friðgeirsdóttir, Katrín Ýr; Carpinelli, Camilla; Isberg, Ari Páll; Helgadóttir, Halla; Arnardóttir, Erna Sif; Saavedra, Jose M.; Islind, Anna Sigridur; Department of Engineering; Department of Sport Science; Department of Computer Science
Background: The demand for sleep interventions is high and steadily growing. Digital therapeutics (DTx) can help individuals improve their sleep remotely, over an extended period, and with less effort from medical professionals. Obstructive sleep apnea (OSA), one of the most prevalent and consequential sleep disorders, can be treated with health-supporting behavior changes, such as physical exercise and weight loss, and, therefore, acts as a promising application for DTx. Objective: The study aimed to analyze a digital intervention from both medical and technological perspectives by moving beyond clinical markers and exploring more deeply how the DTx application was used. This study aimed to propose a novel way in which association rules can function as an exploratory tool to analyze the sleep, behavior, and engagement of participants with the DTx application on a day-to-day level. Methods: A lifestyle intervention study (N=192) targeted at adults with mild-to-moderate OSA aimed to reduce their OSA severity using a DTx application and an exercise program over a study period of 12 weeks. The participants’ OSA severity was assessed through polysomnography at the beginning and at the end of the study period, and the participants tracked their sleep with a digital sleep diary and a smartwatch over the course of the entire study. The DTx application provided data on when and how the participants pursued the proposed lifestyle interventions. These heterogeneous data sources were combined into one multimodal dataset, which was explored through descriptive statistics. Ultimately, the data were turned into a transaction-based format, and association rules were derived using the Apriori algorithm. Results: Analyzing the participants’ interaction with the application revealed the lifestyle interventions they pursued and how their behavior and sleep patterns changed over time. The Apriori algorithm generated a set of association rules with lift and confidence scores that were significantly higher than those for the co-occurrence of items through random chance. The rules show co-occurrence of missions and items from the sleep diary, as well as items derived from the watch measurements. Conclusions: The study showed the richness of the various data sources provided by a digital intervention using wearables and how they can be used to get an in-depth understanding of the study. The generated association rules showed the presence of significant co-occurrences across the different data modalities and highlighted their effectiveness as an exploratory tool for multimodal health data.
Verk
Making Software Development More Diverse and Inclusive : Key Themes, Challenges, and Future Directions
(2025-05-27) Hyrynsalmi, Sonja M.; Baltes, Sebastian; Brown, Chris; Prikladnicki, Rafael; Rodriguez-Perez, Gema; Serebrenik, Alexander; Simmonds, Jocelyn; Trinkenreich, Bianca; Wang, Yi; Liebel, Grischa; Department of Computer Science
Introduction: Digital products increasingly reshape industries, influencing human behavior and decision-making. However, the software development teams developing these systems often lack diversity, which may lead to designs that overlook the needs, equal treatment or safety of diverse user groups. These risks highlight the need for fostering diversity and inclusion in software development to create safer, more equitable technology. Method: This research is based on insights from an academic meeting in June 2023 involving 23 software engineering researchers and practitioners. We used the collaborative discussion method 1-2-4-ALL as a systematic research approach and identified six themes around the theme “challenges and opportunities to improve Software Developer Diversity and Inclusion (SDDI).” We identified benefits, harms, and future research directions for the four main themes. Then, we discuss the remaining two themes, AI & SDDI and AI & Computer Science education, which have a cross-cutting effect on the other themes. Results: This research explores the key challenges and research opportunities for promoting SDDI, providing a roadmap to guide both researchers and practitioners. We underline that research around SDDI requires a constant focus on maximizing benefits while minimizing harms, especially to vulnerable groups. As a research community, we must strike this balance in a responsible way.

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