Discovering cell types using manifold learning and enhanced visualization of single-cell RNA-Seq data

Identifying relevant disease modules such as target cell types is a significant step for studying diseases. High-throughput single-cell RNA-Seq (scRNA-seq) technologies have advanced in recent years, enabling researchers to investigate cells individually and understand their biological mechanisms. Computational techniques such as clustering, are the most suitable approach in scRNA-seq data analysis when the cell types have not been well-characterized. These techniques can be used to identify a group of genes that belong to a specific cell type based on their similar gene expression patterns. However, due to the sparsity and high-dimensionality of scRNA-seq data, classical clustering methods are not efficient. Therefore, the use of non-linear dimensionality reduction techniques to improve clustering results is crucial. We introduce a method that is used to identify representative clusters of different cell types by combining non-linear dimensionality reduction techniques and clustering algorithms. We assess the impact of different dimensionality reduction techniques combined with the clustering of thirteen publicly available scRNA-seq datasets of different tissues, sizes, and technologies. We further performed gene set enrichment analysis to evaluate the proposed method’s performance. As such, our results show that modified locally linear embedding combined with independent component analysis yields overall the best performance relative to the existing unsupervised methods across different datasets.

Surrogate-Enhanced Parameter Inference for Function-Valued Models

We present an approach to enhance the performance and flexibility of the Bayesian inference of model parameters based on observations of the measured data. Going beyond the usual surrogate-enhanced Monte-Carlo or optimization methods that focus on a scalar loss, we place emphasis on a function-valued output of a formally infinite dimension. For this purpose, the surrogate models are built on a combination of linear dimensionality reduction in an adaptive basis of principal components and Gaussian process regression for the map between reduced feature spaces. Since the decoded surrogate provides the full model output rather than only the loss, it is re-usable for multiple calibration measurements as well as different loss metrics and, consequently, allows for flexible marginalization over such quantities and applications to Bayesian hierarchical models. We evaluate the method’s performance based on a case study of a toy model and a simple riverine diatom model for the Elbe river. As input data, this model uses six tunable scalar parameters as well as silica concentrations in the upper reach of the river together with the continuous time-series of temperature, radiation, and river discharge over a specific year. The output consists of continuous time-series data that are calibrated against corresponding measurements from the Geesthacht Weir station at the Elbe river. For this study, only two scalar inputs were considered together with a function-valued output and compared to an existing model calibration using direct simulation runs without a surrogate.

Analyzing Grid-Based Direct Quantum Molecular Dynamics Using Non-Linear Dimensionality Reduction

Grid-based schemes for simulating quantum dynamics, such as the multi-configuration time-dependent Hartree (MCTDH) method, provide highly accurate predictions of the coupled nuclear and electronic dynamics in molecular systems. Such approaches provide a multi-dimensional, time-dependent view of the system wavefunction represented on a coordinate grid; in the case of non-adiabatic simulations, additional information about the state populations adds a further layer of complexity. As such, wavepacket motion on potential energy surfaces which couple many nuclear and electronic degrees-of-freedom can be extremely challenging to analyse in order to extract physical insight beyond the usual expectation-value picture. Here, we show that non-linear dimensionality reduction (NLDR) methods, notably diffusion maps, can be adapted to extract information from grid-based wavefunction dynamics simulations, providing insight into key nuclear motions which explain the observed dynamics. This approach is demonstrated for 2-D and 9-D models of proton transfer in salicylaldimine, as well as 8-D and full 12-D simulations of cis-trans isomerization in ethene; these simulations demonstrate how NLDR can provide alternative views of wavefunction dynamics, and also highlight future developments.

Discovering Key Topics From Short, Real-World Medical Inquiries via Natural Language Processing

Millions of unsolicited medical inquiries are received by pharmaceutical companies every year. It has been hypothesized that these inquiries represent a treasure trove of information, potentially giving insight into matters regarding medicinal products and the associated medical treatments. However, due to the large volume and specialized nature of the inquiries, it is difficult to perform timely, recurrent, and comprehensive analyses. Here, we combine biomedical word embeddings, non-linear dimensionality reduction, and hierarchical clustering to automatically discover key topics in real-world medical inquiries from customers. This approach does not require ontologies nor annotations. The discovered topics are meaningful and medically relevant, as judged by medical information specialists, thus demonstrating that unsolicited medical inquiries are a source of valuable customer insights. Our work paves the way for the machine-learning-driven analysis of medical inquiries in the pharmaceutical industry, which ultimately aims at improving patient care.

On Topological Analysis of fs-LIMS Data. Implications for in Situ Planetary Mass Spectrometry

In this contribution, we present results of non-linear dimensionality reduction and classification of the fs laser ablation ionization mass spectrometry (LIMS) imaging dataset acquired from the Precambrian Gunflint chert (1.88 Ga) using a miniature time-of-flight mass spectrometer developed for in situ space applications. We discuss the data generation, processing, and analysis pipeline for the classification of the recorded fs-LIMS mass spectra. Further, we define topological biosignatures identified for Precambrian Gunflint microfossils by projecting the recorded fs-LIMS intensity space into low dimensions. Two distinct subtypes of microfossil-related spectra, a layer of organic contamination and inorganic quartz matrix were identified using the fs-LIMS data. The topological analysis applied to the fs-LIMS data allows to gain additional knowledge from large datasets, formulate hypotheses and quickly generate insights from spectral data. Our contribution illustrates the utility of applying spatially resolved mass spectrometry in combination with topology-based analytics in detecting signatures of early (primitive) life. Our results indicate that fs-LIMS, in combination with topological methods, provides a powerful analytical framework and could be applied to the study of other complex mineralogical samples.

Non-linear dimensionality reduction on extracellular waveforms reveals cell type diversity in premotor cortex

Cortical circuits are thought to contain a large number of cell types that coordinate to produce behavior. Current in vivo methods rely on clustering of specified features of extracellular waveforms to identify putative cell types, but these capture only a small amount of variation. Here, we develop a new method (WaveMAP) that combines non-linear dimensionality reduction with graph clustering to identify putative cell types. We apply WaveMAP to extracellular waveforms recorded from dorsal premotor cortex of macaque monkeys performing a decision-making task. Using WaveMAP, we robustly establish eight waveform clusters and show that these clusters recapitulate previously identified narrow- and broad-spiking types while revealing previously unknown diversity within these subtypes. The eight clusters exhibited distinct laminar distributions, characteristic firing rate patterns, and decision-related dynamics. Such insights were weaker when using featurebased approaches. WaveMAP therefore provides a more nuanced understanding of the dynamics of cell types in cortical circuits.

Research on Outlier Detection for High-Dimensional Data Based on PPCLOF

Aiming at the “dimension disaster” problem encountered in the outlier detection of high-dimensional data, this paper uses the projection pursuit algorithm to perform non-linear dimensionality reduction on high-dimensional data by calculating the phase relationship between dimensions. According to the sample points obtained by dimensionality reduction, the LOF (Local Outlier Factor) algorithm is applied to calculate the outlier factor to obtain the relevant outlier data. In order to improve the calculation accuracy and efficiency of the LOF algorithm, clustering method is used to cut the outlier calculation data to reduce the amount of calculation. Experiments on real-world and artificial datasets, compared with the existing algorithms, demonstrated the effectiveness and efficiency of the proposed algorithm.

Nonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome

The stomach is inhabited by diverse microbial communities, co-existing in a dynamic balance. Long-term use of drugs such as proton pump inhibitors (PPIs), or bacterial infection such as Helicobacter pylori, cause significant microbial alterations. Yet, studies revealing how the commensal bacteria re-organize, due to these perturbations of the gastric environment, are in early phase and rely principally on linear techniques for multivariate analysis. Here we disclose the importance of complementing linear dimensionality reduction techniques with nonlinear ones to unveil hidden patterns that remain unseen by linear embedding. Then, we prove the advantages to complete multivariate pattern analysis with differential network analysis, to reveal mechanisms of bacterial network re-organizations which emerge from perturbations induced by a medical treatment (PPIs) or an infectious state (H. pylori). Finally, we show how to build bacteria-metabolite multilayer networks that can deepen our understanding of the metabolite pathways significantly associated to the perturbed microbial communities.