arXiv Quantitative Biology @arxiv_bio@qoto.org

Multimodal neuroimaging modeling has becomes a widely used approach but confronts considerable challenges due to heterogeneity, which encompasses variability in data types, scales, and formats across modalities. This variability necessitates the deployment of advanced computational methods to integrate and interpret these diverse datasets within a cohesive analytical framework. In our research, we amalgamate functional magnetic resonance imaging, diffusion tensor imaging, and structural MRI into a cohesive framework. This integration capitalizes on the unique strengths of each modality and their inherent interconnections, aiming for a comprehensive understanding of the brain's connectivity and anatomical characteristics. Utilizing the Glasser atlas for parcellation, we integrate imaging derived features from various modalities: functional connectivity from fMRI, structural connectivity from DTI, and anatomical features from sMRI within consistent regions. Our approach incorporates a masking strategy to differentially weight neural connections, thereby facilitating a holistic amalgamation of multimodal imaging data. This technique enhances interpretability at connectivity level, transcending traditional analyses centered on singular regional attributes. The model is applied to the Human Connectome Project's Development study to elucidate the associations between multimodal imaging and cognitive functions throughout youth. The analysis demonstrates improved predictive accuracy and uncovers crucial anatomical features and essential neural connections, deepening our understanding of brain structure and function.

Changes in the number of copies of certain parts of the genome, known as copy number alterations (CNAs), due to somatic mutation processes are a hallmark of many cancers. This genomic complexity is known to be associated with poorer outcomes for patients but describing its contribution in detail has been difficult. Copy number alterations can affect large regions spanning whole chromosomes or the entire genome itself but can also be localised to only small segments of the genome and no methods exist that allow this multi-scale nature to be quantified. In this paper, we address this using Wave-LSTM, a signal decomposition approach designed to capture the multi-scale structure of complex whole genome copy number profiles. Using wavelet-based source separation in combination with deep learning-based attention mechanisms. We show that Wave-LSTM can be used to derive multi-scale representations from copy number profiles which can be used to decipher sub-clonal structures from single-cell copy number data and to improve survival prediction performance from patient tumour profiles.

Significance: Cerebral blood flow (CBF) imaging is crucial for diagnosing cerebrovascular diseases. However, existing large neuroimaging techniques with high cost, low sampling rate, and poor mobility make them unsuitable for continuous and longitudinal CBF monitoring at the bedside. Aim: This study aimed to develop a low-cost, portable, programmable scanning diffuse speckle contrast imaging (PS-DSCI) technology for fast, high-density, and depth-sensitive imaging of CBF in rodents. Approach: The PS-DSCI employed a programmable digital micromirror device (DMD) for remote line-shape laser (785 nm) scanning on tissue surface and synchronized a 2D camera for capturing boundary diffuse laser speckle contrasts. New algorithms were developed to address deformations of line-shape scanning, thus minimizing CBF reconstruction artifacts. The PS-DSCI was examined in head-simulating phantoms and adult mice. Results: The PS-DSCI enables resolving Intralipid particle flow contrasts at different tissue depths. In vivo experiments in adult mice demonstrated the capability of PS-DSCI to image global/regional CBF variations induced by 8% CO2 inhalation and transient carotid artery ligations. Conclusions: Compared to conventional point scanning, the line scanning in PS-DSCI significantly increases spatiotemporal resolution. The high sampling rate of PS-DSCI is crucial for capturing rapid CBF changes while high spatial resolution is important for visualizing brain vasculature.

Do neural network models of vision learn brain-aligned representations because they share architectural constraints and task objectives with biological vision or because they learn universal features of natural image processing? We characterized the universality of hundreds of thousands of representational dimensions from visual neural networks with varied construction. We found that networks with varied architectures and task objectives learn to represent natural images using a shared set of latent dimensions, despite appearing highly distinct at a surface level. Next, by comparing these networks with human brain representations measured with fMRI, we found that the most brain-aligned representations in neural networks are those that are universal and independent of a network's specific characteristics. Remarkably, each network can be reduced to fewer than ten of its most universal dimensions with little impact on its representational similarity to the human brain. These results suggest that the underlying similarities between artificial and biological vision are primarily governed by a core set of universal image representations that are convergently learned by diverse systems.

We present a mathematical model of lophotrichous bacteria, motivated by Pseudomonas putida, which swim through fluid by rotating a cluster of multiple flagella extended from near one pole of the cell body. Although the flagella rotate individually, they are typically bundled together, enabling the bacterium to exhibit three primary modes of motility: push, pull, and wrapping. One key determinant of these modes is the coordination between motor torque and rotational direction of motors. The computational variations in this coordination reveal a wide spectrum of dynamical motion regimes, which are modulated by hydrodynamic interactions between flagellar filaments. These dynamic modes can be categorized into two groups based on the collective behavior of flagella, i.e., bundled and unbundled configurations. For some of these configurations, experimental examples from fluorescence microscopy recordings of swimming P. putida cells are also presented. Furthermore, we analyze the characteristics of stable bundles, such as push and pull, and investigate the dependence of swimming behaviors on the elastic properties of the flagella.

Phylogenetic networks are graphs that are used to represent evolutionary relationships between different taxa. They generalize phylogenetic trees since for example, unlike trees, they permit lineages to combine. Recently, there has been rising interest in semi-directed phylogenetic networks, which are mixed graphs in which certain lineage combination events are represented by directed edges coming together, whereas the remaining edges are left undirected. One reason to consider such networks is that it can be difficult to root a network using real data. In this paper, we consider the problem of when a semi-directed phylogenetic network is defined or encoded by the smaller networks that it induces on the $4$-leaf subsets of its leaf set. These smaller networks are called quarnets. We prove that semi-directed binary level-$2$ phylogenetic networks are encoded by their quarnets, but that this is not the case for level-$3$. In addition, we prove that the so-called blob tree of a semi-directed binary network, a tree that gives the coarse-grained structure of the network, is always encoded by the quarnets of the network.

The concept of personalised medicine in cancer therapy is becoming increasingly important. There already exist drugs administered specifically for patients with tumours presenting well-defined mutations. However, the field is still in its infancy, and personalised treatments are far from being standard of care. Personalised medicine is often associated with the utilisation of omics data. Yet, implementation of multi-omics data has proven difficult, due to the variety and scale of the information within the data, as well as the complexity behind the myriad of interactions taking place within the cell. An alternative approach to precision medicine is to employ a function-based profile of the cell. This involves screening a range of drugs against patient derived cells. Here we demonstrate a proof-of-concept, where a collection of drug screens against a highly diverse set of patient-derived cell lines, are leveraged to identify putative treatment options for a 'new patient'. We show that this methodology is highly efficient in ranking the drugs according to their activity towards the target cells. We argue that this approach offers great potential, as activities can be efficiently imputed from various subsets of the drug treated cell lines that do not necessarily originate from the same tissue type.

Hi-C sequencing is widely used for analyzing chromosomal interactions. In this study, we propose "superimposed Hi-C" which features paired EcoP15I sites in a linker to facilitate sticky-end ligation with target DNAs. Superimposed Hi-C overcomes Hi-C's technical limitations, enabling the identification of single cell's chromosomal interactions.

This paper gives an introduction to \textit{Cognidynamics}, that is to the dynamics of cognitive systems driven by optimal objectives imposed over time when they interact either with a defined virtual or with a real-world environment. The proposed theory is developed in the general framework of dynamic programming which leads to think of computational laws dictated by classic Hamiltonian equations. Those equations lead to the formulation of a neural propagation scheme in cognitive agents modeled by dynamic neural networks which exhibits locality in both space and time, thus contributing the longstanding debate on biological plausibility of learning algorithms like Backpropagation. We interpret the learning process in terms of energy exchange with the environment and show the crucial role of energy dissipation and its links with focus of attention mechanisms and conscious behavior.

As deep learning systems are scaled up to many billions of parameters, relating their internal structure to external behaviors becomes very challenging. Although daunting, this problem is not new: Neuroscientists and cognitive scientists have accumulated decades of experience analyzing a particularly complex system - the brain. In this work, we argue that interpreting both biological and artificial neural systems requires analyzing those systems at multiple levels of analysis, with different analytic tools for each level. We first lay out a joint grand challenge among scientists who study the brain and who study artificial neural networks: understanding how distributed neural mechanisms give rise to complex cognition and behavior. We then present a series of analytical tools that can be used to analyze biological and artificial neural systems, organizing those tools according to Marr's three levels of analysis: computation/behavior, algorithm/representation, and implementation. Overall, the multilevel interpretability framework provides a principled way to tackle neural system complexity; links structure, computation, and behavior; clarifies assumptions and research priorities at each level; and paves the way toward a unified effort for understanding intelligent systems, may they be biological or artificial.

This study investigates the causal relationships between Clinical Dementia Ratings (CDR) and its six domain scores across two distinct aging datasets: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Longitudinal Aging Study of India (LASI). Using Directed Acyclic Graphs (DAGs) derived from Bayesian network models, we analyze the dependencies among domain scores and their influence on the global CDR. Our approach leverages the PC algorithm to estimate the DAG structures for both datasets, revealing notable differences in causal relationships and edge strengths between the Western and Indian populations. The analysis highlights a stronger dependency of CDR scores on memory functions in both datasets, but with significant variations in edge strengths and node degrees. By contrasting these findings, we aim to elucidate population-specific differences and similarities in dementia progression, providing insights that could inform targeted interventions and improve understanding of dementia across diverse demographic contexts.

Motivation: Biologists who want to analyse their single-cell transcriptomics dataset must install and use specialist software via the command line. This is often impractical for non-bioinformaticians. Whilst CELLxGENE provides an intuitive graphical interface to facilitate analysis outside the command line, its server-side installation and execution remain complex. A version that is easier to install and run would allow non-bioinformaticians to take advantage of this valuable tool without needing to use the command line. Results: Portable-CELLxGENE is a standalone distribution of CELLxGENE that can be installed via a graphical interface. It contains an easy-to-use extension of the CELLxGENE-gateway Python package to allow the analysis of multiple datasets. Availability and implementation: Standalone executables compiled for Windows and MacOS are available at github.com/george-hall-ucl/portable-cellxgene. Source code is also available at the same address. Licensed under the GNU GPL v3.

Recent advances in self-supervised learning enabled novel medical AI models, known as foundation models (FMs) that offer great potential for characterizing health from diverse biomedical data. Continuous glucose monitoring (CGM) provides rich, temporal data on glycemic patterns, but its full potential for predicting broader health outcomes remains underutilized. Here, we present GluFormer, a generative foundation model on biomedical temporal data based on a transformer architecture, and trained on over 10 million CGM measurements from 10,812 non-diabetic individuals. We tokenized the CGM training data and trained GluFormer using next token prediction in a generative, autoregressive manner. We demonstrate that GluFormer generalizes effectively to 15 different external datasets, including 4936 individuals across 5 different geographical regions, 6 different CGM devices, and several metabolic disorders, including normoglycemic, prediabetic, and diabetic populations, as well as those with gestational diabetes and obesity. GluFormer produces embeddings which outperform traditional CGM analysis tools, and achieves high Pearson correlations in predicting clinical parameters such as HbA1c, liver-related parameters, blood lipids, and sleep-related indices. Notably, GluFormer can also predict onset of future health outcomes even 4 years in advance. We also show that CGM embeddings from pre-intervention periods in Randomized Clinical Trials (RCTs) outperform other methods in predicting primary and secondary outcomes. When integrating dietary data into GluFormer, we show that the enhanced model can accurately generate CGM data based only on dietary intake data, simulate outcomes of dietary interventions, and predict individual responses to specific foods. Overall, we show that GluFormer accurately predicts health outcomes which generalize across different populations metabolic conditions.

Nutrients are critical to the functioning of the human body and their imbalance can result in detrimental health concerns. The majority of nutritional literature focuses on macronutrients, often ignoring the more critical nuances of micronutrient balance, which require more precise regulation. Currently, micronutrient status is routinely assessed via complex methods that are arduous for both the patient and the clinician. To address the global burden of micronutrient malnutrition, innovations in assessment must be accessible and noninvasive. In support of this task, this article synthesizes useful background information on micronutrients themselves, reviews the state of biofluid and physiological analyses for their assessment, and presents actionable opportunities to push the field forward. By taking a unique, clinical perspective that is absent from technological research on the topic, we find that the state of the art suffers from limited clinical relevance, a lack of overlap between biofluid and physiological approaches, and highly invasive and inaccessible solutions. Future work has the opportunity to maximize the impact of a novel assessment method by incorporating clinical relevance, the holistic nature of micronutrition, and prioritizing accessible and noninvasive systems.

This study explores prosodic production in latent aphasia, a mild form of aphasia associated with left-hemisphere brain damage (e.g. stroke). Unlike prior research on moderate to severe aphasia, we investigated latent aphasia, which can seem to have very similar speech production with neurotypical speech. We analysed the f0, intensity and duration of utterance-initial and utterance-final words of ten speakers with latent aphasia and ten matching controls. Regression models were fitted to improve our understanding of this understudied type of very mild aphasia. The results highlighted varying degrees of differences in all three prosodic measures between groups. We also investigated the diagnostic classification of latent aphasia versus neurotypical control using random forest, aiming to build a fast and reliable tool to assist with the identification of latent aphasia. The random forest analysis also reinforced the significance of prosodic features in distinguishing latent aphasia.

Sleep staging is critical for assessing sleep quality and diagnosing disorders. Recent advancements in artificial intelligence have driven the development of automated sleep staging models, which still face two significant challenges. 1) Simultaneously extracting prominent temporal and spatial sleep features from multi-channel raw signals, including characteristic sleep waveforms and salient spatial brain networks. 2) Capturing the spatial-temporal coupling patterns essential for accurate sleep staging. To address these challenges, we propose a novel framework named ST-USleepNet, comprising a spatial-temporal graph construction module (ST) and a U-shaped sleep network (USleepNet). The ST module converts raw signals into a spatial-temporal graph to model spatial-temporal couplings. The USleepNet utilizes a U-shaped structure originally designed for image segmentation. Similar to how image segmentation isolates significant targets, when applied to both raw sleep signals and ST module-generated graph data, USleepNet segments these inputs to extract prominent temporal and spatial sleep features simultaneously. Testing on three datasets demonstrates that ST-USleepNet outperforms existing baselines, and model visualizations confirm its efficacy in extracting prominent sleep features and temporal-spatial coupling patterns across various sleep stages. The code is available at: https://github.com/Majy-Yuji/ST-USleepNet.git.

Introduction: Electrical impedance spectroscopy (EIS) has recently developed as a novel diagnostic device for screening and evaluating cervical dysplasia, prostate cancer, breast cancer and basal cell carcinoma. The current study aimed to validate and evaluate bioimpedance as a diagnostic tool for tobacco-induced oral lesions. Methodology: The study comprised 50 OSCC and OPMD tissue specimens for in-vitro study and 320 subjects for in vivo study. Bioimpedance device prepared and calibrated. EIS measurements were done for the habit and control groups and were compared. Results: The impedance value in the control group was significantly higher compared to the OPMD and OSCC groups. Diagnosis based on BIS measurements has a sensitivity of 95.9% and a specificity of 86.7%. Conclusion: Bioimpedance device can help in decision-making for differentiating OPMD and OSCC cases and their management, especially in primary healthcare settings. Keywords: Impedance, Cancer, Diagnosis, Device, Community

Understanding how the brain represents and processes information is crucial for advancing neuroscience and artificial intelligence. Representational similarity analysis (RSA) has been instrumental in characterizing neural representations, but traditional RSA relies solely on geometric properties, overlooking crucial topological information. This thesis introduces Topological RSA (tRSA), a novel framework combining geometric and topological properties of neural representations. tRSA applies nonlinear monotonic transforms to representational dissimilarities, emphasizing local topology while retaining intermediate-scale geometry. The resulting geo-topological matrices enable model comparisons robust to noise and individual idiosyncrasies. This thesis introduces several key methodological advances: (1) Topological RSA (tRSA) for identifying computational signatures and testing topological hypotheses; (2) Adaptive Geo-Topological Dependence Measure (AGTDM) for detecting complex multivariate relationships; (3) Procrustes-aligned Multidimensional Scaling (pMDS) for revealing neural computation stages; (4) Temporal Topological Data Analysis (tTDA) for uncovering developmental trajectories; and (5) Single-cell Topological Simplicial Analysis (scTSA) for characterizing cell population complexity. Through analyses of neural recordings, biological data, and neural network simulations, this thesis demonstrates the power and versatility of these methods in understanding brains, computational models, and complex biological systems. They not only offer robust approaches for adjudicating among competing models but also reveal novel theoretical insights into the nature of neural computation. This work lays the foundation for future investigations at the intersection of topology, neuroscience, and time series analysis, paving the way for more nuanced understanding of brain function and dysfunction.

Since the start of the coronavirus-19 pandemic, the use of wastewater-based epidemiology (WBE) for disease surveillance has increased throughout the world. Because wastewater measurements are affected by external factors, processing WBE data typically includes a normalization step in order to adjust wastewater measurements (e.g. viral RNA concentrations) to account for variation due to dynamic population changes, sewer travel effects, or laboratory methods. Pepper mild mottle virus (PMMoV), a plant RNA virus abundant in human feces and wastewater, has been used as a fecal contamination indicator and has been used to normalize wastewater measurements extensively. However, there has been little work to characterize the spatio-temporal variability of PMMoV in wastewater, which may influence the effectiveness of PMMoV for adjusting or normalizing WBE measurements. Here, we investigate its variability across space and time using data collected over a two-year period from sewage treatment plants across the United States. We find that most variation in PMMoV measurements can be attributed to longitude and latitude followed by site-specific variables. Further research into cross-geographical and -temporal comparability of PMMoV-normalized pathogen concentrations would strengthen the utility of PMMoV in WBE.

Single-cell analysis is an increasingly relevant approach in "omics'' studies. In the last decade, it has been applied to various fields, including cancer biology, neuroscience, and, especially, developmental biology. This rise in popularity has been accompanied with creation of modern software, development of new pipelines and design of new algorithms. Many established algorithms have also been applied with varying levels of effectiveness. Currently, there is an abundance of algorithms for all steps of the general workflow. While some scientists use ready-made pipelines (such as Seurat), manual analysis is popular, too, as it allows more flexibility. Scientists who perform their own analysis face multiple options when it comes to the choice of algorithms. We have used two different datasets to test some of the most widely-used algorithms. In this paper, we are going to report the main differences between them, suggest a minimal number of algorithms for each step, and explain our suggestions. In certain stages, it is impossible to make a clear choice without further context. In these cases, we are going to explore the major possibilities, and make suggestions for each one of them.