PERMEPSY: a multicentre, randomized, double-blind proof-of-concept trial of personalized metacognitive training for adults with psychosis — a study protocol
Maria Lamarca, Maria Lamarca, Maria Lamarca
et al.
BackgroundWhile psychological interventions are effective at improving symptoms of psychosis, accessible, cost- and time-efficient treatments remain limited. Personalized medicine has emerged as a promising approach, tailoring interventions to individual needs. Metacognitive Training (MCT), with its established efficacy and adaptable format, is well-suited for personalization. The PERMEPSY project (Towards a Personalized Medicine Approach to Psychological Treatment for Psychosis) aims to deliver tailored MCT intervention for individuals with psychosis.MethodsPERMEPSY is an international study funded by ERAPerMed (JTC2022) involving five clinical partners (Spain, Chile, France, Germany, Poland) and one technological partner (Spain). The project involves a proof-of-concept clinical trial recruiting 51 participants from each center for a total of 255 adult participants with psychosis in a prospective study (Registration: NCT06603922, 19-09-2024). The trial will test the efficacy of a Machine Learning (ML)-derived platform at predicting clinical and functional outcomes from baseline scores and compare a personalized MCT (P-MCT) to a classical MCT based on the platform’s predictions.AimsPERMEPSY seeks to (1) develop and test the predictive power of an algorithm that could support decision-making, and (2) ascertain whether P-MCT is more effective than MCT at improving key symptoms and cognitive impairments associated to psychosis.ResultsA harmonized retrospective database enabled the development of a predictive ML algorithm, integrated into an innovative platform. This platform provides clinicians with the information needed to deliver P-MCT. Predictions include changes in positive symptoms (e.g., delusions), insight, self-esteem, and treatment adherence.DiscussionBy integrating diverse data types and innovative technology, PERMEPSY addresses the need for personalized, effective treatment in psychosis, aiming to reduce individual and systemic burdens while supporting clinicians in their decision-making.
A Biologically Interpretable Cognitive Architecture for Online Structuring of Episodic Memories into Cognitive Maps
E. A. Dzhivelikian, A. I. Panov
Cognitive maps provide a powerful framework for understanding spatial and abstract reasoning in biological and artificial agents. While recent computational models link cognitive maps to hippocampal-entorhinal mechanisms, they often rely on global optimization rules (e.g., backpropagation) that lack biological plausibility. In this work, we propose a novel cognitive architecture for structuring episodic memories into cognitive maps using local, Hebbian-like learning rules, compatible with neural substrate constraints. Our model integrates the Successor Features framework with episodic memories, enabling incremental, online learning through agent-environment interaction. We demonstrate its efficacy in a partially observable grid-world, where the architecture autonomously organizes memories into structured representations without centralized optimization. This work bridges computational neuroscience and AI, offering a biologically grounded approach to cognitive map formation in artificial adaptive agents.
Mind Meets Space: Rethinking Agentic Spatial Intelligence from a Neuroscience-inspired Perspective
Bui Duc Manh, Soumyaratna Debnath, Zetong Zhang
et al.
Recent advances in agentic AI have led to systems capable of autonomous task execution and language-based reasoning, yet their spatial reasoning abilities remain limited and underexplored, largely constrained to symbolic and sequential processing. In contrast, human spatial intelligence, rooted in integrated multisensory perception, spatial memory, and cognitive maps, enables flexible, context-aware decision-making in unstructured environments. Therefore, bridging this gap is critical for advancing Agentic Spatial Intelligence toward better interaction with the physical 3D world. To this end, we first start from scrutinizing the spatial neural models as studied in computational neuroscience, and accordingly introduce a novel computational framework grounded in neuroscience principles. This framework maps core biological functions to six essential computation modules: bio-inspired multimodal sensing, multi-sensory integration, egocentric-allocentric conversion, an artificial cognitive map, spatial memory, and spatial reasoning. Together, these modules form a perspective landscape for agentic spatial reasoning capability across both virtual and physical environments. On top, we conduct a framework-guided analysis of recent methods, evaluating their relevance to each module and identifying critical gaps that hinder the development of more neuroscience-grounded spatial reasoning modules. We further examine emerging benchmarks and datasets and explore potential application domains ranging from virtual to embodied systems, such as robotics. Finally, we outline potential research directions, emphasizing the promising roadmap that can generalize spatial reasoning across dynamic or unstructured environments. We hope this work will benefit the research community with a neuroscience-grounded perspective and a structured pathway. Our project page can be found at Github.
Unleashing the power of computational insights in revealing the complexity of biological systems in the new era of spatial multi-omics
Zhiwei Fan, Tiangang Wang, Kexin Huang
et al.
Recent advances in spatial omics technologies have revolutionized our ability to study biological systems with unprecedented resolution. By preserving the spatial context of molecular measurements, these methods enable comprehensive mapping of cellular heterogeneity, tissue architecture, and dynamic biological processes in developmental biology, neuroscience, oncology, and evolutionary studies. This review highlights a systematic overview of the continuous advancements in both technology and computational algorithms that are paving the way for a deeper, more systematic comprehension of the structure and mechanisms of mammalian tissues and organs by using spatial multi-omics. Our viewpoint demonstrates how advanced machine learning algorithms and multi-omics integrative modeling can decode complex biological processes, including the spatial organization and topological relationships of cells during organ development, as well as key molecular signatures and regulatory networks underlying tumorigenesis and metastasis. Finally, we outline future directions for technological innovation and modeling insights of spatial omics in precision medicine.
In-silico biological discovery with large perturbation models
Djordje Miladinovic, Tobias Höppe, Mathieu Chevalley
et al.
Data generated in perturbation experiments link perturbations to the changes they elicit and therefore contain information relevant to numerous biological discovery tasks -- from understanding the relationships between biological entities to developing therapeutics. However, these data encompass diverse perturbations and readouts, and the complex dependence of experimental outcomes on their biological context makes it challenging to integrate insights across experiments. Here, we present the Large Perturbation Model (LPM), a deep-learning model that integrates multiple, heterogeneous perturbation experiments by representing perturbation, readout, and context as disentangled dimensions. LPM outperforms existing methods across multiple biological discovery tasks, including in predicting post-perturbation transcriptomes of unseen experiments, identifying shared molecular mechanisms of action between chemical and genetic perturbations, and facilitating the inference of gene-gene interaction networks.
An accessible and efficient mobile eye-tracking application for community-based cognitive impairment screening in China
Mingxia Wei, Jincheng Li, Tongyao You
et al.
Abstract Background Cognitive impairment (CI) poses a major global health challenge. In China, neuropsychological scales, regarded as the gold standard for cognitive diagnosis, are largely inaccessible in resource-limited communities. The Mobile Eye-Tracking Application (m-ETA), which captures and quantifies eye movement features, has emerged as a promising tool for CI screening. Methods We developed a tablet-based m-ETA using a two-step approach. First, a logistic regression (LR) model was trained to discriminate dementia based on six oculometric features in a hospital cohort (N = 204), and regression analyses were conducted to validate the biological relevance of these features with Alzheimer’s Disease–related phenotypes in an exploratory dataset (N = 101). Second, the generalizability and accuracy of the LR model were externally validated in a community-based cohort (N = 433) and further evaluated in two real-world community populations (N = 2,685). Model performance was assessed using sensitivity, specificity, negative predictive value (NPV), and area under the ROC curve (AUC). Results m-ETA achieved high diagnostic accuracy for dementia (AUC = 0.99). Regression analyses confirmed that the m-ETA-derived oculometric features were significantly associated with cognitive performance, brain atrophy, and tau deposition in the exploratory dataset (all P < 0.05). m-ETA accurately detected CI (AUC = 0.80), with excellent negative predictive value for ruling out CI, and identified individuals with lower cognition performance across diverse communities. Conclusions m-ETA offers a low-cost, non-invasive, and efficient tool for large-scale CI screening, particularly suited to underserved and low-literacy communities in China.
Neurosciences. Biological psychiatry. Neuropsychiatry, Neurology. Diseases of the nervous system
Bibliometric Mapping of Research Trends and Hotspots of Microglia in Spinal Cord Injury (2000–2024)
Ziming Cai, Gongpeng Xiong, Jintao Wu
et al.
ABSTRACT Introduction Spinal cord injury (SCI), acknowledged as the most severe complication arising from spinal trauma, pertains to the dysfunction of the spinal cord due to traumatic events or other pathological conditions. Extensive research has elucidated a substantial correlation between SCI and inflammatory processes, highlighting the critical involvement of microglia in orchestrating neuroinflammatory responses. Moreover, a growing body of evidence has demonstrated a strong connection between microglial activation and both the pathogenesis and progression of SCI. Objective We chose bibliometric analysis to comprehensively summarize the research progress of microglia in SCI, aiming to provide researchers with current trends and future research directions. Methods All articles and reviews addressing microglia in SCI were systematically retrieved from the Web of Science Core Collection database, spanning publications from 2000 to 2024. Subsequent bibliometric analysis was conducted utilizing four analytical tools: VOSviewer (version 1.6.20), R software (package bibliometrix), the Biblioshiny web interface, and CiteSpace (version 6.2.R4), ensuring comprehensive examination of publication patterns and research trends. Results A total of 2428 publications were ultimately included in this bibliometric analysis. The annual publication count demonstrated a consistent upward trajectory. China is the country with the most published articles, and Ohio State University ranks first in institutional publications. Experimental Neurology is the journal with the most published articles, while Journal of Neuroscience is the journal with the most cited articles. Popovich Pg is the author with the highest productivity and co‐citation. Cluster analysis yielded a total of 15 different co‐citation clusters. Time analysis shows explosive citation outbreaks in 2006, 2009, and 2011. Keyword analysis revealed inflammation, expression, activation, and central nervous system as the most frequently occurring terms. Recent keyword trends feature emerging terms like exosomes, extracellular vesicles, and nanoparticles. Keyword bursts revealed promotes, extracellular vesicle, recovery, neuroinflammation, therapy, polarization, and pathway are the hotspots of research at the present stage and are likely to continue. These findings provide critical insights for developing microglia‐targeted therapeutic strategies and prioritizing research directions in neuroinflammatory modulation to improve functional recovery after SCI. Conclusion Emerging research frontiers prominently feature exosomes, gut microbiota, and nanoparticles. The interplay between microglia‐mediated neuroinflammation and SCI has emerged as a critical focal point in current scientific investigations and is anticipated to remain central to forthcoming scientific inquiries.
Neurosciences. Biological psychiatry. Neuropsychiatry
Decline in activities of daily living in the rarer dementias
Sebastian Crutch, Claire Waddington, Emma Harding
et al.
Rarer dementias are associated with atypical symptoms and younger onset, which result in a higher burden of care. We provide a review of the global literature on longitudinal decline in activities of daily living (ADLs) in dementias that account for less than 10% of dementia diagnoses. Published studies were identified through searches conducted in Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (Embase), Excerpta Medica Care (Emcare), PsycINFO, and Cumulative Index in Nursing and Allied Health Literature (CINAHL). The search criteria included terms related to ‘rarer dementias’, ‘activities of daily living’ and ‘longitudinal or cross-sectional studies’ following a predefined protocol registered. Studies were screened, and those that met the criteria were citation searched. Quality assessments were performed, and relevant data were extracted. 20 articles were selected, of which 19 focused on dementias within the frontotemporal dementia/primary progressive aphasia spectrum, while one addressed posterior cortical atrophy. Four studies were cross-sectional and 16 studies were longitudinal, with a median duration of 2.2 years. The Disability Assessment for Dementia was used to measure decline in 8 of the 20 studies. The varied sequences of ADL decline reported in the literature reflect variation in diagnostic specificity between studies and within-syndrome heterogeneity. Most studies used Alzheimer’s disease staging scales to measure decline, which cannot capture variant-specific symptoms. To enhance care provision in dementia, ADL scales could be deployed postdiagnosis to aid treatment and planning. This necessitates staging scales that are variant-specific and span the disease course from diagnosis to end of life. PROSPERO registration number: CRD42021283302.
Conformal Prediction in Dynamic Biological Systems
Alberto Portela, Julio R. Banga, Marcos Matabuena
Uncertainty quantification (UQ) is the process of systematically determining and characterizing the degree of confidence in computational model predictions. In the context of systems biology, especially with dynamic models, UQ is crucial because it addresses the challenges posed by nonlinearity and parameter sensitivity, allowing us to properly understand and extrapolate the behavior of complex biological systems. Here, we focus on dynamic models represented by deterministic nonlinear ordinary differential equations. Many current UQ approaches in this field rely on Bayesian statistical methods. While powerful, these methods often require strong prior specifications and make parametric assumptions that may not always hold in biological systems. Additionally, these methods face challenges in domains where sample sizes are limited, and statistical inference becomes constrained, with computational speed being a bottleneck in large models of biological systems. As an alternative, we propose the use of conformal inference methods, introducing two novel algorithms that, in some instances, offer non-asymptotic guarantees, enhancing robustness and scalability across various applications. We demonstrate the efficacy of our proposed algorithms through several scenarios, highlighting their advantages over traditional Bayesian approaches. The proposed methods show promising results for diverse biological data structures and scenarios, offering a general framework to quantify uncertainty for dynamic models of biological systems.The software for the methodology and the reproduction of the results is available at https://zenodo.org/doi/10.5281/zenodo.13644870.
Launching Your VR Neuroscience Laboratory
Ying Choon Wu, Christopher Maymon, Jonathon Paden
et al.
The proliferation and refinement of affordable virtual reality (VR) technologies and wearable sensors have opened new frontiers in cognitive and behavioral neuroscience. This chapter offers a broad overview of VR for anyone interested in leveraging it as a research tool. In the first section, it examines the fundamental functionalities of VR and outlines important considerations that inform the development of immersive content that stimulates the senses. In the second section, the focus of the discussion shifts to the implementation of VR in the context of the neuroscience lab. Practical advice is offered on adapting commercial, off-theshelf devices to specific research purposes. Further, methods are explored for recording, synchronizing, and fusing heterogeneous forms of data obtained through the VR system or add-on sensors, as well as for labeling events and capturing game play.
COMPASS: Computational Mapping of Patient-Therapist Alliance Strategies with Language Modeling
Baihan Lin, Djallel Bouneffouf, Yulia Landa
et al.
The therapeutic working alliance is a critical predictor of psychotherapy success. Traditionally, working alliance assessment relies on questionnaires completed by both therapists and patients. In this paper, we present COMPASS, a novel framework to directly infer the therapeutic working alliance from the natural language used in psychotherapy sessions. Our approach leverages advanced large language models (LLMs) to analyze session transcripts and map them to distributed representations. These representations capture the semantic similarities between the dialogues and psychometric instruments, such as the Working Alliance Inventory. Analyzing a dataset of over 950 sessions spanning diverse psychiatric conditions -- including anxiety (N=498), depression (N=377), schizophrenia (N=71), and suicidal tendencies (N=12) -- collected between 1970 and 2012, we demonstrate the effectiveness of our method in providing fine-grained mapping of patient-therapist alignment trajectories, offering interpretable insights for clinical practice, and identifying emerging patterns related to the condition being treated. By employing various deep learning-based topic modeling techniques in combination with prompting generative language models, we analyze the topical characteristics of different psychiatric conditions and how these topics evolve during each turn of the conversation. This integrated framework enhances the understanding of therapeutic interactions, enables timely feedback for therapists on the quality of therapeutic relationships, and provides clear, actionable insights to improve the effectiveness of psychotherapy.
Circulating blood circular RNA in Parkinson’s Disease; from involvement in pathology to diagnostic tools in at-risk individuals
Aleksandra Beric, Yichen Sun, Santiago Sanchez
et al.
Abstract To identify circRNAs associated with Parkinson’s disease (PD) we leveraged two of the largest publicly available studies with longitudinal clinical and blood transcriptomic data. We performed a cross-sectional study utilizing the last visit of each participant (N = 1848), and a longitudinal analysis that included 1166 participants with at least two time points. We identified 192 differentially expressed circRNAs, with effects that were sustained during disease, in mutation carriers, and diverse ancestry. The 192 circRNAs were leveraged to distinguish between PD and healthy participants with a ROC AUC of 0.797. Further, 71 circRNAs were sufficient to distinguish between genetic PD (AUC71 = 0.954) and, at-risk participants (AUC71 = 0.929) and healthy controls, supporting that circRNAs have the potential to aid the diagnosis of PD. Finally, we identified five circRNAs highly correlated with symptom severity. Overall, we demonstrated that circRNAs play an important role in PD and can be clinically relevant to improve diagnostic and monitoring.
Neurology. Diseases of the nervous system
The prevalence of bruxism in children with profound intellectual and multiple disabilities; a systematic review and meta-analysis
Robert J. Goddard, Wim P. Krijnen, Vincent Roelfsema
et al.
Introduction: Bruxism is a repetitive masticatory muscle activity that may cause substantial morbidity and reduce the quality of life in children with profound intellectual and multiple disabilities. Assessment methods most commonly used were caregiver reporting and dental examination, This systematic review with meta-analysis aims to determine the prevalence of bruxism in children with profound intellectual and multiple disabilities and to describe the currently used assessment methods for bruxism in this population. Methods: We conducted a systematic review and meta-analysis using a multi-component search strategy. We used a random effects model to calculate the prevalence and 95 % confidence intervals for each study, for all studies combined, and specifically for Rett syndrome (RS), cerebral palsy (CP), Down syndrome (DS), and “other disorders (primarily Angelman syndrome and Prader–Willi syndrome).” Results: The prevalence for the entire group based on a random effects model was found to be 49 % (95 %CI 41–57 %) with high heterogeneity (I2 = 93 %, p < 0.01), for RS 74 % (95 %CI 53–88 %, I2 = 84 %, p < 0.01), CP 48 % (95 %CI 38–57 %, I2 = 86 %, p < 0.01), DS 40 % (95 %CI 33–47 %, I2 = 60 %, p < 0.01) and “other disorders” 40 % (95 %CI 18–67 %, I2 = 98 %, p < 0.01). The group prevalences were not equal, indicating a significant difference (P-value = 0.03), with a notably higher likelihood of RS. Conclusion: We observed a five-fold increased likelihood of bruxism in children with profound intellectual and multiple disabilities. The disorder with the highest prevalence was Rett syndrome, with a seven-fold increased likelihood of bruxism. The increased likelihood of bruxism in this vulnerable group of children demands clinicians pay heed to this substantial morbidity.
Neurology. Diseases of the nervous system
Postoperative Depression: Insight, Screening, Diagnosis, and Treatment of Choice
Risza Subiantoro, Margarita M Maramis, Nining Febriana
et al.
Introduction: Postoperative depression is a condition of depressive effects in patients without symptoms of depressive mood that occurs a few weeks after surgery and persists for at least 2 weeks. It generally possesses the same symptoms as major depressive disorder. Review: Their difference is that surgery is the trigger of depression in postoperative depression cases. Postoperative depression is associated with increased patients’ morbidity and mortality, increased the risk of disease complications, reduced postoperative healing process, prolonged the duration of treatment, and reduced patients’ quality of life. Therefore, mental health conditions should always be assessed on patients after undergoing surgery. Postoperative depression therapy needs to consider the benefits of antidepressants and adequate pain management. Antidepressant considerations also need to consider interactions with other drugs. Psychotherapy and cognitive behavioral therapy are also useful in postoperative depression management. Conclusion: This review is aimed to give insight about postoperative depression, its importance, and how to treat it.
Psychology, Neurosciences. Biological psychiatry. Neuropsychiatry
Large-scale Foundation Models and Generative AI for BigData Neuroscience
Ran Wang, Zhe Sage Chen
Recent advances in machine learning have made revolutionary breakthroughs in computer games, image and natural language understanding, and scientific discovery. Foundation models and large-scale language models (LLMs) have recently achieved human-like intelligence thanks to BigData. With the help of self-supervised learning (SSL) and transfer learning, these models may potentially reshape the landscapes of neuroscience research and make a significant impact on the future. Here we present a mini-review on recent advances in foundation models and generative AI models as well as their applications in neuroscience, including natural language and speech, semantic memory, brain-machine interfaces (BMIs), and data augmentation. We argue that this paradigm-shift framework will open new avenues for many neuroscience research directions and discuss the accompanying challenges and opportunities.
Neuroscience needs Network Science
Dániel L Barabási, Ginestra Bianconi, Ed Bullmore
et al.
The brain is a complex system comprising a myriad of interacting elements, posing significant challenges in understanding its structure, function, and dynamics. Network science has emerged as a powerful tool for studying such intricate systems, offering a framework for integrating multiscale data and complexity. Here, we discuss the application of network science in the study of the brain, addressing topics such as network models and metrics, the connectome, and the role of dynamics in neural networks. We explore the challenges and opportunities in integrating multiple data streams for understanding the neural transitions from development to healthy function to disease, and discuss the potential for collaboration between network science and neuroscience communities. We underscore the importance of fostering interdisciplinary opportunities through funding initiatives, workshops, and conferences, as well as supporting students and postdoctoral fellows with interests in both disciplines. By uniting the network science and neuroscience communities, we can develop novel network-based methods tailored to neural circuits, paving the way towards a deeper understanding of the brain and its functions.
A Mechanistic Insight into Sources of Error of Visual Working Memory in Multiple Sclerosis (PP-01)
Ali Motahharynia, Ahmad Pourmohammadi, Armin Adibi
et al.
Working memory (WM) is one of the most affected cognitive domains in multiple sclerosis (MS), which is mainly studied by the previously established binary model for information storage (slot model). However, recent observations based on the continuous reproduction paradigms have shown that assuming dynamic allocation of WM resources (resource model) instead of the binary hypothesis will give more accurate predictions in WM assessment. Moreover, continuous reproduction paradigms allow for assessing the distribution of error in recalling information, providing new insights into the organization of the WM system. Hence, by utilizing two continuous reproduction paradigms, memory-guided localization (MGL) and analog recall task with sequential presentation, we investigated WM dysfunction in MS. Our results demonstrated an overall increase in recall error and decreased recall precision in MS. While sequential paradigms were better in distinguishing healthy control from relapsing-remitting MS, MGL were more accurate in discriminating MS subtypes (relapsing-remitting from secondary progressive), providing evidence about the underlying mechanisms of WM deficit in progressive states of the disease. Furthermore, computational modeling of the results from the sequential paradigm determined that imprecision in decoding information and swap error (mistakenly reporting the feature of other presented items) were responsible for WM dysfunction in MS. Overall, this study offered a sensitive measure for assessing WM deficit and provided new insight into the organization of the WM system in MS population.
Neurology. Diseases of the nervous system
Schrodinger dynamics and Berry phase of undulatory locomotion
Alexander E. Cohen, Alasdair D. Hastewell, Sreeparna Pradhan
et al.
Spectral mode representations play an essential role in various areas of physics, from quantum mechanics to fluid turbulence, but they are not yet extensively used to characterize and describe the behavioral dynamics of living systems. Here, we show that mode-based linear models inferred from experimental live-imaging data can provide an accurate low-dimensional description of undulatory locomotion in worms, centipedes, robots, and snakes. By incorporating physical symmetries and known biological constraints into the dynamical model, we find that the shape dynamics are generically governed by Schrodinger equations in mode space. The eigenstates of the effective biophysical Hamiltonians and their adiabatic variations enable the efficient classification and differentiation of locomotion behaviors in natural, simulated, and robotic organisms using Grassmann distances and Berry phases. While our analysis focuses on a widely studied class of biophysical locomotion phenomena, the underlying approach generalizes to other physical or living systems that permit a mode representation subject to geometric shape constraints.
en
physics.bio-ph, cond-mat.soft
Biological connectomes as a representation for the architecture of artificial neural networks
Samuel Schmidgall, Catherine Schuman, Maryam Parsa
Grand efforts in neuroscience are working toward mapping the connectomes of many new species, including the near completion of the Drosophila melanogaster. It is important to ask whether these models could benefit artificial intelligence. In this work we ask two fundamental questions: (1) where and when biological connectomes can provide use in machine learning, (2) which design principles are necessary for extracting a good representation of the connectome. Toward this end, we translate the motor circuit of the C. Elegans nematode into artificial neural networks at varying levels of biophysical realism and evaluate the outcome of training these networks on motor and non-motor behavioral tasks. We demonstrate that biophysical realism need not be upheld to attain the advantages of using biological circuits. We also establish that, even if the exact wiring diagram is not retained, the architectural statistics provide a valuable prior. Finally, we show that while the C. Elegans locomotion circuit provides a powerful inductive bias on locomotion problems, its structure may hinder performance on tasks unrelated to locomotion such as visual classification problems.
An Optimal Likelihood Free Method for Biological Model Selection
Vincent D. Zaballa, Elliot E. Hui
Systems biology seeks to create math models of biological systems to reduce inherent biological complexity and provide predictions for applications such as therapeutic development. However, it remains a challenge to determine which math model is correct and how to arrive optimally at the answer. We present an algorithm for automated biological model selection using mathematical models of systems biology and likelihood free inference methods. Our algorithm shows improved performance in arriving at correct models without a priori information over conventional heuristics used in experimental biology and random search. This method shows promise to accelerate biological basic science and drug discovery.