Understanding how genes are regulated is fundamental to many biological research questions. While experimental and computational methods allow us to identify which genes can interact with each other, finding the polarity of these interactions (whether activation or repression) is a non-trivial problem. We introduce sc-GRIP (Single-cell Gene Regulation Interaction Polarity), a graph convolutional framework that infers the directionality of transcription factor gene interactions directly from single-cell RNA data. By combining gene expression profiles with gene interaction graphs, sc-GRIP learns latent representations of genes and predicts regulatory polarity using a bilinear decoder. Our method enables scalable, cell-type-specific inference without relying on prior species-specific annotations or extensive biological validation. We demonstrate sc-GRIP's effectiveness on curated datasets from human and mouse, and show the advantages over other methods. sc-GRIP particularly excels in the usage on non-model organisms, and we provide a case study on a morphologically simple animal, Suberites domuncula, where sc-GRIP manages to expand our understanding of gene regulations. sc-GRIP offers a novel computational approach for reconstructing biologically interpretable regulatory networks, not only in well-studied organisms but especially in emerging organisms, where large-scale experimental setups are often unfeasible.

Detecting arbitrarily shaped clusters in high-dimensional noisy data is challenging for current clustering methods. We introduce SHADE, the first deep clustering algorithm that incorporates density-connectivity into its loss function. Similar to existing deep clustering algorithms, SHADE supports high-dimensional and large data sets with the expressive power of a deep autoencoder. In contrast to most existing deep clustering methods that rely on a centroid-based clustering objective, SHADE incorporates a novel loss function that captures density-connectivity. It thereby learns a representation that enhances the separation of density-connected clusters. SHADE detects a stable clustering and noise points fully automatically without any user input. It outperforms existing methods in clustering quality, especially on data that contain non-Gaussian clusters, such as video data. Moreover, the embedded space of SHADE is suitable for visualization and interpretation of the clustering results as the individual shapes of the clusters are preserved.

Causal Feature Learning (CFL) infers macro-level causes (e.g., an aggregation of pixels in a traffic light image) from micro-level data (e.g., pixels of the image) by clustering the predicted probabilities of effect states (e.g., state of the traffic light). The current method for CFL uses a two-step procedure. First, a classifier for the effect states is trained, and afterwards, the predicted effect state probabilities are clustered. With CaFe DBSCAN, we present a novel density-based clustering method that conducts CFL directly by estimating conditional probabilities during clustering. To this end, we introduce the notion of clustering regions with similar conditional probabilities of the effect states given their micro-level data points. Our single-step approach has the following benefits: (1) CaFe DBSCAN introduces a comprehensive approach to Causal Feature Learning. Unlike existing methods, CaFe DBSCAN uses a probabilistic framework and does not require separate classification and clustering steps implemented by different algorithms relying on various assumptions, parameter settings, and optimization goals. (2) We do not need to train and tune a classifier first, hence the algorithm is more runtime-efficient than the current approach. (3) Due to the properties of density-based clustering algorithms, CaFe DBSCAN is robust against noise and outliers, which leads to purer clusters. (4) Our algorithm automatically infers a reasonable number of clusters, i.e., macro-level causes. We demonstrate the benefits of CaFe DBSCAN on synthetic and real-world data.

The field of deep clustering combines deep learning and clustering to learn representations that improve both the learned representation and the performance of the considered clustering method. Most existing deep clustering methods are designed for a single clustering method, e.g., k-means, spectral clustering, or Gaussian mixture models, but it is well known that no clustering algorithm works best in all circumstances. Consensus clustering tries to alleviate the individual weaknesses of clustering algorithms by building a consensus between members of a clustering ensemble. Currently, there is no deep clustering method that can include multiple heterogeneous clustering algorithms in an ensemble to update representations and clusterings together. To close this gap, we introduce the idea of a consensus representation that maximizes the agreement between ensemble members. Further, we propose DECCS (Deep Embedded Clustering with Consensus representationS), a deep consensus clustering method that learns a consensus representation by enhancing the embedded space to such a degree that all ensemble members agree on a common clustering result. Our contributions are the following: (1) We introduce the idea of learning consensus representations for heterogeneous clusterings, a novel notion to approach consensus clustering. (2) We propose DECCS, the first deep clustering method that jointly improves the representation and clustering results of multiple heterogeneous clustering algorithms. (3) We show in experiments that learning a consensus representation with DECCS is outperforming several relevant baselines from deep clustering and consensus clustering.