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Arend, L.

Publications and source records attributed to Arend, L..

5 recordsLinked to original sources

POME: Graph-based embeddings for partially observed mixed-type data

Partially observed mixed-type (POM) data, as often encountered in clinical, epidemiological, and phenotypic datasets, are very common in biomedical research. Yet, advanced data analysis and machine learning based on POM data is complicated by their heterogeneous nature and often substantial fractions of missing values. While one promising way to overcome these issues is to compute vector-valued embeddings for POM datasets which can then be used for downstream analyses, existing embedding methods are mostly not designed for POM data. To address this gap, we developed POME (partially observed mixed-type data embeddings), a self-supervised model that yields low-dimensional representations of both samples and variables, using shared concept learning and a bipartite graph representation of the underlying POM data. We validated POME through extensive experiments on three real-world biomedical datasets, with diverse downstream tasks and objectives: POME achieves state-of-the-art imputation performance and produces high-quality patient representations that support not only unsupervised discovery of well-separated and clinically meaningful patients subgroups but also supervised predictive modeling and zero-shot representation space mining for use cases such as adjuvant therapy modality recommendation. POME is available as a Python package on GitHub (https://github.com/bionetslab/POME) and PyPI (https://pypi.org/project/pome-py).

bioinformatics↗

Bridging the gap between genome-wide association studies and network medicine with GNExT

MotivationA growing volume of large-scale genome-wide association study (GWAS) datasets offers unprecedented power to uncover the genetic determinants of complex traits, but existing web-based platforms for GWAS data exploration provide limited support for interpreting these findings within broader biological systems. Systems medicine is particularly well-suited to fill this gap, as its network-oriented view of molecular interactions enables the integration of genetic signals into coherent network modules, thereby opening opportunities for disease mechanism mining and drug repurposing. ResultsWe introduce GNExT (GWAS Network Exploration Tool), a web-based platform that significantly extends the scope of exploration of variant-level effects and significance beyond those provided by existing solutions. By including MAGMA and Drugst.One, GNExT allows its users to study genetic variants in the context of the latest systems medicine approaches, extending to the identification of potential drug repurposing candidates. Moreover, GNExT advances platform implementation well beyond the current state of the art by offering a highly standardized Nextflow pipeline for data import and preprocessing, allowing researchers to deploy their study results on a sophisticated web interface with minimal implementation overhead. We demonstrate the utility of GNExT using a genome-wide association meta-analysis of human olfactory identification, in which the framework translated isolated GWAS signals to potential pharmacological targets in human olfaction. Furthermore, the deployment of a GNExT instance on European-ancestry Pan-UK Biobank data demonstrates the frameworks scalability, resulting in a comprehensive large-scale resource encompassing thousands of traits and enabling new network medicine-based investigations. Availability and ImplementationThe complete GNExT ecosystem, including the Nextflow preprocessing pipeline, the backend service, and frontend interface, is publicly available on GitHub (https://github.com/dyhealthnet/gnext_nf_pipeline, https://github.com/dyhealthnet/gnext_platform). The public instances of the GNExT platform on olfaction and Pan-UKBB are available under https://olfaction.gnext.gm.eurac.edu and https://panukbb-eur.gnext.gm.eurac.edu.

bioinformatics↗

Systematic Evaluation of Normalization Approaches in Tandem Mass Tag and Label-Free Protein Quantification Data Using PRONE

Despite the significant progress in accuracy and reliability in mass spectrometry technology, as well as the development of strategies based on isotopic labeling or internal standards in recent decades, systematic biases originating from non-biological factors remain a significant challenge in data analysis. In addition, the wide range of available normalization methods renders the choice of a suitable normalization method challenging. We systematically evaluated 17 normalization and two batch effect correction methods, originally developed for pre-processing DNA microarray data but widely applied in proteomics, on six publicly available spike-in and three label-free and tandem mass tag datasets. Opposed to state-of-the-art normalization practice, we found that a reduction in intragroup variation is not directly related to the effectiveness of the normalization methods. Furthermore, our results demonstrated that the methods RobNorm and Normics, specifically developed for proteomics data, in line with LoessF performed consistently well across the spike-in datasets, while EigenMS exhibited a high false positive rate. Finally, based on experimental data, we show that normalization substantially impacts downstream analyses, and the impact is highly dataset-specific, emphasizing the importance of use-case-specific evaluations for novel proteomics datasets. For this, we developed the PROteomics Normalization Evaluator (PRONE), a unifying R package enabling comparative evaluation of normalization methods, including their impact on downstream analyses, while offering considerable flexibility, acknowledging the lack of universally accepted standards. PRONE is available on Bioconductor with a web application accessible at https://exbio.wzw.tum.de/prone/.

bioinformatics↗

Neural Manifold Capacity Captures Representation Geometry, Correlations, and Task-Efficiency Across Species and Behaviors

From an eagle spotting a fish in shimmering water to a scientist extracting patterns from noisy data, many cognitive tasks require untangling overlapping signals. Neural circuits achieve this by transforming complex sensory inputs into distinct, separable representations that guide behavior. Data-visualization techniques convey the geometry of these transformations, and decoding approaches quantify performance efficiency. However, we lack a framework for linking these two key aspects. Here we address this gap by introducing a data-driven analysis framework, which we call Geometry Linked to Untangling Efficiency (GLUE) with manifold capacity theory, that links changes in the geometrical properties of neural activity patterns to representational untangling at the computational level. We applied GLUE to over seven neuroscience datasets--spanning multiple organisms, tasks, and recording techniques--and found that task-relevant representations untangle in many domains, including along the cortical hierarchy, through learning, and over the course of intrinsic neural dynamics. Furthermore, GLUE can characterize the underlying geometric mechanisms of representational untangling, and explain how it facilitates efficient and robust computation. Beyond neuroscience, GLUE provides a powerful framework for quantifying information organization in data-intensive fields such as structural genomics and interpretable AI, where analyzing high-dimensional representations remains a fundamental challenge.

neuroscience↗

A Systematic Comparison of Differential Analysis Methods for CyTOF Data

Cytometry techniques are widely used to discover cellular characteristics at single-cell resolution. Many data analysis methods for cytometry data focus solely on identifying subpopulations via clustering and testing for differential cell abundance. For differential expression analysis of markers between conditions, only few tools exist. These tools either reduce the data distribution to medians, discarding valuable information, or have underlying assumptions that may not hold for all expression patterns. Here, we systematically evaluated existing and novel approaches for differential expression analysis on real and simulated CyTOF data. We found that methods using median marker expressions compute fast and reliable results when the data is not strongly zero-inflated. Methods using all data detect changes in strongly zero-inflated markers, but partially suffer from overprediction or cannot handle big datasets. We present a new method, CyEMD, based on calculating the Earth Movers Distance between expression distributions that can handle strong zero-inflation without being too sensitive. Additionally, we developed CYANUS, a user-friendly R Shiny App allowing the user to analyze cytometry data with state-of-the-art tools, including well-performing methods from our comparison. A public web interface is available at https://exbio.wzw.tum.de/cyanus/.

bioinformatics↗