Characterization of gene expression patterns in mild cognitive impairment using a transcriptomics approach and neuroimaging endophenotypes.

INTRODUCTION: Identification of novel therapeutics and risk assessment in early stages of Alzheimer's disease (AD) is a crucial aspect of addressing this complex disease. We characterized gene-expression patterns at the mild cognitive impairment (MCI) stage to identify critical mRNA measures and gene clusters associated with AD pathogenesis. METHODS: We used a transcriptomics approach, integrating magnetic resonance imaging (MRI) and peripheral blood-based gene expression data using persistent homology (PH) followed by kernel-based clustering. RESULTS: We identified three clusters of genes significantly associated with diagnosis of amnestic MCI. The biological processes associated with each cluster were mitochondrial function, NF-kB signaling, and apoptosis. Cluster-level associations with cortical thickness displayed canonical AD-like patterns. Driver genes from clusters were also validated in an external dataset for prediction of amyloidosis and clinical diagnosis. DISCUSSION: We found a disease-relevant transcriptomic signature sensitive to prodromal AD and identified a subset of potential therapeutic targets associated with AD pathogenesis.

Topological analysis of differential effects of ketamine and propofol anaesthesia on brain dynamics.

Research has found that the vividness of conscious experience is related to brain dynamics. Despite both being anaesthetics, propofol and ketamine produce different subjective states: we explore the different effects of these two anaesthetics on the structure of dynamic attractors reconstructed from electrophysiological activity recorded from cerebral cortex of two macaques. We used two methods: the first embeds the recordings in a continuous high-dimensional manifold on which we use topological data analysis to infer the presence of higher-order dynamics. The second reconstruction, an ordinal partition network embedding, allows us to create a discrete state-transition network, which is amenable to information-theoretic analysis and contains rich information about state-transition dynamics. We find that the awake condition generally had the 'richest' structure, visiting the most states, the presence of pronounced higher-order structures, and the least deterministic dynamics. By contrast, the propofol condition had the most dissimilar dynamics, transitioning to a more impoverished, constrained, low-structure regime. The ketamine condition, interestingly, seemed to combine aspects of both: while it was generally less complex than the awake condition, it remained well above propofol in almost all measures. These results provide deeper and more comprehensive insights than what is typically gained by using point-measures of complexity.

Topological gene expression networks recapitulate brain anatomy and function.

Understanding how gene expression translates to and affects human behavior is one of the ultimate goals of neuroscience. In this paper, we present a pipeline based on Mapper, a topological simplification tool, to analyze gene co-expression data. We first validate the method by reproducing key results from the literature on the Allen Human Brain Atlas and the correlations between resting-state fMRI and gene co-expression maps. We then analyze a dopamine-related gene set and find that co-expression networks produced by Mapper return a structure that matches the well-known anatomy of the dopaminergic pathway. Our results suggest that network based descriptions can be a powerful tool to explore the relationships between genetic pathways and their association with brain function and its perturbation due to illness and/or pharmacological challenges.

Construction of and efficient sampling from the simplicial configuration model.

Simplicial complexes are now a popular alternative to networks when it comes to describing the structure of complex systems, primarily because they encode multinode interactions explicitly. With this new description comes the need for principled null models that allow for easy comparison with empirical data. We propose a natural candidate, the simplicial configuration model. The core of our contribution is an efficient and uniform Markov chain Monte Carlo sampler for this model. We demonstrate its usefulness in a short case study by investigating the topology of three real systems and their randomized counterparts (using their Betti numbers). For two out of three systems, the model allows us to reject the hypothesis that there is no organization beyond the local scale.

Navigating features: a topologically informed chart of electromyographic features space.

The success of biological signal pattern recognition depends crucially on the selection of relevant features. Across signal and imaging modalities, a large number of features have been proposed, leading to feature redundancy and the need for optimal feature set identification. A further complication is that, due to the inherent biological variability, even the same classification problem on different datasets can display variations in the respective optimal sets, casting doubts on the generalizability of relevant features. Here, we approach this problem by leveraging topological tools to create charts of features spaces. These charts highlight feature sub-groups that encode similar information (and their respective similarities) allowing for a principled and interpretable choice of features for classification and analysis. Using multiple electromyographic (EMG) datasets as a case study, we use this feature chart to identify functional groups among 58 state-of-the-art EMG features, and to show that they generalize across three different forearm EMG datasets obtained from able-bodied subjects during hand and finger contractions. We find that these groups describe meaningful non-redundant information, succinctly recapitulating information about different regions of feature space. We then recommend representative features from each group based on maximum class separability, robustness and minimum complexity.