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Biology subjects

Nickel, M.

Publications and source records attributed to Nickel, M..

2 recordsLinked to original sources

Poincare Maps for Analyzing Complex Hierarchies in Single-Cell Data

The need to understand cell developmental processes spawned a plethora of computational methods for discovering hierarchies from scRNAseq data. However, existing techniques are based on Euclidean geometry, a suboptimal choice for modeling complex cell trajectories with multiple branches. To overcome this fundamental representation issue we propose Poincare maps, a method that harness the power of hyperbolic geometry into the realm of single-cell data analysis. Often understood as a continuous extension of trees, hyperbolic geometry enables the embedding of complex hierarchical data in only two dimensions while preserving the pairwise distances between points in the hierarchy. This enables direct exploratory analysis and the use of our embeddings in a wide variety of downstream data analysis tasks, such as visualization, clustering, lineage detection and pseudo-time inference. When compared to existing methods --unable to address all these important tasks using a single embedding-- Poincare maps produce state-of-the-art two-dimensional representations of cell trajectories on multiple scRNAseq datasets. More specifically, we demonstrate that Poincare maps allow in a straightforward manner to formulate new hypotheses about biological processes unbeknown to prior methods. Significance statementThe discovery of hierarchies in biological processes is central to developmental biology. We propose Poincare maps, a new method based on hyperbolic geometry to discover continuous hierarchies from pairwise similarities. We demonstrate the efficacy of our method on multiple single-cell datasets on tasks such as visualization, clustering, lineage identification, and pseudo-time inference.

bioinformatics

Brain dysfunction in chronic pain patients assessed by resting-state electroencephalography

Chronic pain is a common and severely disabling disease whose treatment is often unsatisfactory. Insights into the brain mechanisms of chronic pain promise to advance the understanding of the underlying pathophysiology and might help to develop disease markers and novel treatments. Here, we systematically and comprehensively exploited the potential of electroencephalography (EEG) to determine abnormalities of brain function during the resting state in chronic pain. To this end, we performed state-of-the-art analyses of oscillatory brain activity, brain connectivity and brain networks in 101 patients of either sex suffering from chronic pain. The results show that global and local measures of brain activity did not differ between chronic pain patients and a healthy control group. However, we observed significantly increased connectivity at theta (4 - 8 Hz) and gamma (> 60 Hz) frequencies in frontal brain areas as well as global network reorganization at gamma frequencies in chronic pain patients. Furthermore, a machine learning algorithm could differentiate between patients and healthy controls with an above-chance accuracy of 57%, mostly based on frontal connectivity. These results implicate increased theta and gamma synchrony in frontal brain areas in the pathophysiology of chronic pain. While substantial challenges concerning accuracy, specificity and validity of potential EEG-based disease markers remain to be overcome, our study identifies abnormal frontal synchrony at theta and gamma frequencies as promising targets for non-invasive brain stimulation and/or neurofeedback approaches.

neuroscience