Biology subjects

Davoudi, S.

Publications and source records attributed to Davoudi, S..

5 recordsLinked to original sources

bioRxiv2026

Neural feature spaces: characterizing the geometry of brain activity across development

The human brain undergoes profound changes from childhood to adulthood. These changes are foundational to cognitive, affective and social development, and measuring them is essential for identifying atypical development. A common approach consists of analyzing metrics derived from brain activity, such as spectral power, aperiodic activity and signal complexity. However, individual metrics are sensitive to external factors unrelated to development, contributing to inconsistent findings in the literature. Moreover, these metrics are not independent; they show some degree of intrinsic redundancy, which itself evolves across development. Here, we propose a novel approach that focuses on the relationships between neural features rather than their values, defining a "neural feature space" that captures the geometry of brain activity. We analyzed the neural feature spaces of children (4-12 years) and adults (30-45 years), based on 128-channel EEG recordings during naturalistic movie viewing. Specifically, we computed a range of spectral, aperiodic and complexity features and quantified pairwise distances between them using latent variable modeling. Neural feature spaces were significantly different between age groups. Notably, high frequency bands were less differentiated in children and distances between spectral and complexity features differed. Crucially, distances were highly stable across tasks, in contrast to feature values, which varied substantially. These findings suggest that the geometry of neural feature spaces provides robust, interpretable markers of neurodevelopment, offering a complementary approach to feature-based analyses.

neuroscience↗

bioRxiv2025

EC-Bench: A Benchmark for Enzyme Commission NumberPrediction

Enzymes are proteins that catalyze specific biochemical reactions in cells. Enzyme Commission (EC) numbers are used to annotate enzymes in a four-level hierarchy that classifies enzymes based on the specific chemical reactions they catalyze. Accurate EC number prediction is essential for understanding enzyme functions. Despite the availability of numerous methods for predicting EC numbers from protein sequences, there is no unified framework for evaluating and studying such methods systematically. This gap limits the ability of the community to identify the most effective approaches for enzyme annotation. We introduce EC-Bench, a benchmark for EC number prediction, consisting of 1) an initial representative set of existing methods (including homology-based, deep learning, contrastive learning, and language model methods), 2) existing and novel accuracy and efficiency performance metrics, and 3) selected datasets to allow for comprehensive comparative study. EC-Bench is open-source and provides a framework for researchers to not only compare among existing methods objectively under uniform conditions, but also to introduce and effectively evaluate performance of new methods in a comparative frame-work. To demonstrate the utility of EC-Bench, we perform extensive experimentation to compare the existing EC number prediction methods and establish their advantages and disadvantages in a variety of prediction tasks, namely "exact EC number prediction", "EC number completion" and (partial or additional) "EC number recommendation". We find wide variation in the performance of different methods, but also subtle but potentially useful differences in the performance of different methods across tasks and for different parts of the EC hierarchy.

bioinformatics↗

bioRxiv2023

mini-MEndR: A miniaturized 96-well predictive assay to evaluate muscle stem cell mediated repair

Functional evaluation of molecules that are predicted to promote stem cell mediated endogenous repair often requires in vivo transplant studies that are low throughput and hinder the rate of discovery. Here, we offer a strategy to rapidly test and prioritize molecules for functional validation studies. We miniaturized, simplified and expanded the functionality of a previously developed muscle endogenous repair (MEndR) in vitro assay that was shown to capture significant events of the first week of the in vivo muscle endogenous repair process. The new "mini-MEndR assay" consists of miniaturized cellulose scaffolds designed to fit in 96-well plates. The scaffold pores are infiltrated with myoblasts encapsulated in a fibrin-based hydrogel to form thin, engineered skeletal muscle tissues. By evaluating multiple commercially available human primary myoblast lines in 2D and 3D culture, we establish quality assurance metrics for cell line selection that standardize myotube template quality. Pre-adsorbing thrombin to the cellulose scaffolds facilitates in situ tissue polymerization, a critical modification that enables users proficient in myoblast culture to rapidly acquire myotube template fabrication expertise. Following the generation of the 3D myotube template, muscle stem cells (MuSCs), enriched from digested mouse skeletal muscle tissue using an improved magnetic-activated cell sorting protocol, are engrafted onto the engineered human muscle template. A regenerative milieu is then introduced by injuring the muscle tissue with a myotoxin. Addition of a known modulator of MuSC mediated repair recapitulates the in vivo outcomes (enhanced muscle production and Pax7+ cell expansion), but only in the presence of both the stem cells and the regenerative milieu. By fluorescently labeling the mouse MuSCs, we demonstrate the feasibility of co-evaluating human and mouse Pax7+ cell responses to drug treatment, thereby expanding the utility of the assay. Importantly, phenotypic data is collected with a high-content imaging system and is analyzed using CellProfiler-based image analysis pipelines. The miniaturized predictive assay offers a simple, scaled platform with which to co-investigate human and mouse skeletal muscle endogenous repair molecular modulators, and thus is a promising strategy to accelerate the muscle endogenous repair discovery pipeline.

bioengineering↗

bioRxiv2019

A 96-well culture platform enables longitudinal analyses of engineered human skeletal muscle microtissue strength

Three-dimensional (3D) in vitro models of human skeletal muscle mimic aspects of native tissue structure and function, thereby providing a promising system for disease modeling, drug discovery or pre-clinical validation, and toxicity testing. Widespread adoption of this research approach is hindered by the lack of an easy-to-use platform that is simple to fabricate and yields arrays of human skeletal muscle micro-tissues (hMMTs) in culture with reproducible physiological responses that can be assayed non-invasively. Here, we describe a design and methods to generate a reusable mold to fabricate a 96-well platform, referred to as MyoTACTIC, that enables bulk production of 3D hMMTs. All 96-wells and all well features are cast in a single step from the reusable mold. Non-invasive calcium transient and contractile force measurements are performed on hMMTs directly in MyoTACTIC, and unbiased force analysis occurs by a custom automated algorithm, allowing for longitudinal studies of function. Characterizations of MyoTACTIC and resulting hMMTs confirms the reproducibility of device fabrication and biological responses. We show that hMMT contractile force mirrors expected responses to compounds shown by others to decrease (dexamethasone, cerivistatin) or increase (IGF-1) skeletal muscle strength. Since MyoTACTIC supports hMMT long-term culture, we evaluated direct influences of pancreatic cancer chemotherapeutics agents on contraction competent human skeletal muscle fibers. A single application of a clinically relevant dose of Irinotecan decreased hMMT contractile force generation, while clear effects on fiber atrophy were observed histologically only at a higher dose. This suggests an off-target effect that may contribute to cancer associated muscle wasting, and highlights the value of the MyoTACTIC platform to non-invasively predict modulators of human skeletal muscle function.

bioengineering↗

bioRxiv2018

Muscle stem cell intramuscular delivery within hyaluronan methylcellulose improves engraftment efficiency and dispersion

Adult skeletal muscle tissue harbors the capacity for self-repair due to the presence of tissue resident muscle stem cells (MuSCs). Advances in the area of prospective MuSC isolation demonstrated the potential of cell transplantation therapy as a regenerative medicine strategy to restore strength and long-term regenerative capacity to aged, injured, or diseased skeletal muscle tissue. However, cell loss during ejection, limits to post-injection proliferation, and poor donor cell dispersion distal to the injection site are amongst hurdles to overcome to maximize MuSC transplant impact. Here, we assess a physical blend of hyaluronan and methylcellulose (HAMC) as a bioactive, shear thinning hydrogel cell delivery system to improve MuSC transplantation efficiency. Using in vivo transplantation studies, we found that the HAMC delivery system results in a >45% increase in the number of donor-derived fibers as compared to saline delivery. Furthermore, we observed a significant improvement in donor fiber dispersion when transplanted MuSCs were delivered in the HAMC hydrogel. Studies to assess primary myoblast and MuSC viability in HAMC culture revealed no differences compared to the media control even when the cells were first ejected through a syringe and needle or exposed to regenerating skeletal muscle extract to mimic the transplantation procedure. However, when we quantified absolute numbers, we found that more cells pass through the syringe and needle when delivered in HAMC. Culture in HAMC also increased the proportion of MuSCs in cell cycle, via a CD44-independent mechanism. An effect on myoblast proliferation was not observed, suggesting a hierarchical effect. Finally, a series of transplant studies indicated that HAMC delivery does not influence passive cell clearance or alter the host immune response, but instead may serve to support in vivo expansion by delaying differentiation following transplant. Therefore, we conclude that MuSC engraftment efficacy is improved by delivering the therapeutic cell population within HAMC.

bioengineering↗