Biology subjects

Pfeifer, B.

Publications and source records attributed to Pfeifer, B..

7 recordsLinked to original sources

bioRxiv2023

Ensemble-GNN: federated ensemble learning with graph neural networks for disease module discovery and classification

Federated learning enables collaboration in medicine, where data is scattered across multiple centers without the need to aggregate the data in a central cloud. While, in general, machine learning models can be applied to a wide range of data types, graph neural networks (GNNs) are particularly developed for graphs, which are very common in the biomedical domain. For instance, a patient can be represented by a protein-protein interaction (PPI) network where the nodes contain the patient-specific omics features. Here, we present our Ensemble-GNN software package, which can be used to deploy federated, ensemble-based GNNs in Python. Ensemble-GNN allows to quickly build predictive models utilizing PPI networks consisting of various node features such as gene expression and/or DNA methylation. We exemplary show the results from a public dataset of 981 patients and 8469 genes from the Cancer Genome Atlas (TCGA).

bioinformatics↗

bioRxiv2022

Interactive explainable AI platform for graph neural networks

BackgroundLack of trust in artificial intelligence (AI) models in medicine is still the key blockage for the use of AI in clinical decision support systems (CDSS). Although AI models are already performing excellently in systems medicine, their black-box nature entails that patient-specific decisions are incomprehensible for the physician. This is especially true for very complex models such as graph neural networks (GNNs), a common state-of-the-art approach to model biological networks such as protein-protein-interaction graphs (PPIs) to predict clinical outcomes. The aim of explainable AI (XAI) algorithms is to "explain" to a human domain expert, which input features, such as genes, influenced a specific recommendation. However, in the clinical domain, it is essential that these explanations lead to some degree of causal understanding by a clinician in the context of a specific application. ResultsWe developed the CLARUS platform, aiming to promote human understanding of GNN predictions by allowing the domain expert to validate and improve the decision-making process. CLARUS enables the visualisation of the patient-specific biological networks used to train and test the GNN model, where nodes and edges correspond to gene products and their interactions, for instance. XAI methods, such as GNNExplainer, compute relevance values for genes and interactions. The CLARUS graph visualisation highlights gene and interaction relevances by color intensity and line thickness, respectively. This enables domain experts to gain deeper insights into the biological network by identifying the most influential sub-graphs and molecular pathways crucial for the decision-making process. More importantly, the expert can interactively alter the patient-specific PPI network based on the acquired understanding and initiate re-prediction or retraining. This interactivity allows to ask manual counterfactual questions and analyse the resulting effects on the GNN prediction. ConclusionTo the best of our knowledge, we present the first interactive XAI platform prototype, CLARUS, that allows not only the evaluation of specific human counterfactual questions based on user-defined alterations of patient PPI networks and a re-prediction of the clinical outcome but also a retraining of the entire GNN after changing the underlying graph structures. The platform is currently hosted by the GWDG on https://rshiny.gwdg.de/apps/clarus/.

bioinformatics↗

bioRxiv2022

Detection and quantification of introgression using Bayesian inference based on conjugate priors

Introgression (the flow of genes between species) is a major force structuring the evolution of genomes, potentially providing raw material for adaptation. Here, we present a versatile Bayesian model selection approach for the detection and quantification of introgression. The proposed df-BF approach builds upon the recently published distance-based df statistic. Unlike df, df-BF takes into account the number of variant sites within a genomic region. The df-BF method quantifies introgression with the inferred{theta} parameter, and at the same time enables weighing the strength of evidence for introgression based on Bayes Factors. To ensure fast computation we make use of conjugate priors with no need for computational demanding MCMC iterations. We compare our method with other approaches including df, fd, and Pattersons D using a wide range of coalescent simulations. Furthermore, we showcase the applicability of the df-BF approach using whole genome mosquito data. Finally, we integrate the new method into the powerful genomics R-package PopGenome.

evolutionary biology↗

bioRxiv2022

GNN-SubNet: disease subnetwork detection with explainable Graph Neural Networks

The tremendous success of graphical neural networks (GNNs) has already had a major impact on systems biology research. For example, GNNs are currently used for drug target recognition in protein-drug interaction networks as well as cancer gene discovery and more. Important aspects whose practical relevance is often underestimated are comprehensibility, interpretability, and explainability. In this work, we present a graph-based deep learning framework for disease subnetwork detection via explainable GNNs. In our framework, each patient is represented by the topology of a protein-protein network (PPI), and the nodes are enriched by molecular multimodal data, such as gene expression and DNA methylation. Therefore, our novel modification of the GNNexplainer for model-wide explanations can detect potential disease subnetworks, which is of high practical relevance. The proposed methods are implemented in the GNN-SubNet Python program, which we have made freely available on our GitHub for the international research community (https://github.com/pievos101/GNN-SubNet).

bioinformatics↗

bioRxiv2020

A hierarchical clustering and data fusion approach for disease subtype discovery

Recent advances in multi-omics clustering methods enable a more fine-tuned separation of cancer patients into clinical relevant clusters. These advancements have the potential to provide a deeper understanding of cancer progression and may facilitate the treatment of cancer patients. Here, we present a simple hierarchical clustering and data fusion approach, named HC-fused, for the detection of disease subtypes. Unlike other methods, the proposed approach naturally reports on the individual contribution of each single-omic to the data fusion process. We perform multi-view simulations with disjoint and disjunct cluster elements across the views to highlight fundamentally different data integration behaviour of various state-of-the-art methods. HC-fused combines the strengths of some recently published methods and shows superior performance on real world cancer data from the TCGA (The Cancer Genome Atlas) database. An R implementation of our method is available on GitHub (pievos101/HC-fused).

bioinformatics↗

bioRxiv2019

Genome Scans for Selection and Introgression based on k-nearest Neighbor Techniques

In recent years, genome-scan methods have been extensively used to detect local signatures of selection and introgression. Here, we introduce a series of versatile genome-scan methods that are based on non-parametric k-nearest neighbors (kNN) techniques, while incorporating pairwise Fixation Index (FST) estimates and pairwise nucleotide differences (dxy) as features. Simulations were performed for both positive directional selection and introgression, with varying parameters, such as recombination rates, population background histories, the proportion of introgression, and the time of gene flow. We find that kNN-based methods perform remarkably well while yielding stable results almost over the entire range of k. We provide a GitHub repository (pievos101/kNN-Genome-Scans) containing R source code to demonstrate how to apply the proposed methods to real-world genomic data using the population genomics R-package PopGenome.

evolutionary biology↗

bioRxiv2017

Estimates of Introgression as a Function of Pairwise Distances

BackgroundResearch over the last 10 years highlights the increasing importance of hybridization between species as a major force structuring the evolution of genomes and potentially providing raw material for adaptation by natural and/or sexual selection. Fueled by research in a few model systems where phenotypic hybrids are easily identified, research into hybridization and introgression (the flow of genes between species) has exploded with the advent of whole-genome sequencing and emerging methods to detect the signature of hybridization at the whole-genome or chromosome level. Amongst these are a general class of methods that utilize patterns of single-nucleotide polymorphisms (SNPs) across a tree as markers of hybridization. These methods have been applied to a variety of genomic systems ranging from butterflies to Neanderthals to detect introgression, however, when employed at a fine genomic scale these methods do not perform well to quantify introgression in small sample windows.\n\nResultsWe introduce a novel method to detect introgression by combining two widely used statistics: pairwise nucleotide diversity dxy and Pattersons D. The resulting statistic, the Basic distance fraction (Bdf), accounts for genetic distance across possible topologies and is designed to simultaneously detect and quantify introgression. We also relate our new method to the recently published fd and incorporate these statistics into the powerful genomics R-package PopGenome, freely available on CRAN. The supplemental material contains a wide range of simulation studies and a detailed manual how to perform the statistics within the PopGenome framework.\n\nConclusionWe present a new distance based statistic Bdf that avoids the pitfalls of Pattersons D when applied to small genomic regions and accurately quantifies the fraction of introgression (f) for a wide range of simulation scenarios.

evolutionary biology↗