Helena Andrés-Terré

Amine Amor, Pietro Lio', Vikash Singh et al.

Combining different modalities of data from human tissues has been critical in advancing biomedical research and personalised medical care. In this study, we leverage a graph embedding model (i.e VGAE) to perform link prediction on tissue-specific Gene-Gene Interaction (GGI) networks. Through ablation experiments, we prove that the combination of multiple biological modalities (i.e multi-omics) leads to powerful embeddings and better link prediction performances. Our evaluation shows that the integration of gene methylation profiles and RNA-sequencing data significantly improves the link prediction performance. Overall, the combination of RNA-sequencing and gene methylation data leads to a link prediction accuracy of 71% on GGI networks. By harnessing graph representation learning on multi-omics data, our work brings novel insights to the current literature on multi-omics integration in bioinformatics.

Dmitry Kazhdan, Botty Dimanov, Helena Andres Terre et al.

Concept-based explanations have emerged as a popular way of extracting human-interpretable representations from deep discriminative models. At the same time, the disentanglement learning literature has focused on extracting similar representations in an unsupervised or weakly-supervised way, using deep generative models. Despite the overlapping goals and potential synergies, to our knowledge, there has not yet been a systematic comparison of the limitations and trade-offs between concept-based explanations and disentanglement approaches. In this paper, we give an overview of these fields, comparing and contrasting their properties and behaviours on a diverse set of tasks, and highlighting their potential strengths and limitations. In particular, we demonstrate that state-of-the-art approaches from both classes can be data inefficient, sensitive to the specific nature of the classification/regression task, or sensitive to the employed concept representation.

Maja Trębacz, Zohreh Shams, Mateja Jamnik et al.

Stratifying cancer patients based on their gene expression levels allows improving diagnosis, survival analysis and treatment planning. However, such data is extremely highly dimensional as it contains expression values for over 20000 genes per patient, and the number of samples in the datasets is low. To deal with such settings, we propose to incorporate prior biological knowledge about genes from ontologies into the machine learning system for the task of patient classification given their gene expression data. We use ontology embeddings that capture the semantic similarities between the genes to direct a Graph Convolutional Network, and therefore sparsify the network connections. We show this approach provides an advantage for predicting clinical targets from high-dimensional low-sample data.

Paul Scherer, Maja Trȩbacz, Nikola Simidjievski et al.

We propose a method for gene expression based analysis of cancer phenotypes incorporating network biology knowledge through unsupervised construction of computational graphs. The structural construction of the computational graphs is driven by the use of topological clustering algorithms on protein-protein networks which incorporate inductive biases stemming from network biology research in protein complex discovery. This structurally constrains the hypothesis space over the possible computational graph factorisation whose parameters can then be learned through supervised or unsupervised task settings. The sparse construction of the computational graph enables the differential protein complex activity analysis whilst also interpreting the individual contributions of genes/proteins involved in each individual protein complex. In our experiments analysing a variety of cancer phenotypes, we show that the proposed methods outperform SVM, Fully-Connected MLP, and Randomly-Connected MLPs in all tasks. Our work introduces a scalable method for incorporating large interaction networks as prior knowledge to drive the construction of powerful computational models amenable to introspective study.

Paul Scherer, Helena Andres-Terre, Pietro Lio et al.

We present two instances, L-GAE and L-VGAE, of the variational graph auto-encoding family (VGAE) based on separating feature propagation operations from graph convolution layers typically found in graph learning methods to a single linear matrix computation made prior to input in standard auto-encoder architectures. This decoupling enables the independent and fixed design of the auto-encoder without requiring additional GCN layers for every desired increase in the size of a node's local receptive field. Fixing the auto-encoder enables a fairer assessment on the size of a nodes receptive field in building representations. Furthermore a by-product of fixing the auto-encoder design often results in substantially smaller networks than their VGAE counterparts especially as we increase the number of feature propagations. A comparative downstream evaluation on link prediction tasks show comparable state of the art performance to similar VGAE arrangements despite considerable simplification. We also show the simple application of our methodology to more challenging representation learning scenarios such as spatio-temporal graph representation learning.

Helena Andrés-Terré, Pietro Lió

The use of Variational Autoencoders in different Machine Learning tasks has drastically increased in the last years. They have been developed as denoising, clustering and generative tools, highlighting a large potential in a wide range of fields. Their embeddings are able to extract relevant information from highly dimensional inputs, but the converged models can differ significantly and lead to degeneracy on the latent space. We leverage the relation between theoretical physics and machine learning to explain this behaviour, and introduce a new approach to correct for degeneration by using perturbation theory. The re-formulation of the embedding as multi-dimensional generative distribution, allows mapping to a new set of functions and their corresponding energy spectrum. We optimise for a perturbed Hamiltonian, with an additional energy potential that is related to the unobserved topology of the data. Our results show the potential of a new theoretical approach that can be used to interpret the latent space and generative nature of unsupervised learning, while the energy landscapes defined by the perturbations can be further used for modelling and dynamical purposes.

Ezra Webb, Ben Day, Helena Andres-Terre et al.

Many complex natural and cultural phenomena are well modelled by systems of simple interactions between particles. A number of architectures have been developed to articulate this kind of structure, both implicitly and explicitly. We consider an unsupervised explicit model, the NRI model, and make a series of representational adaptations and physically motivated changes. Most notably we factorise the inferred latent interaction graph into a multiplex graph, allowing each layer to encode for a different interaction-type. This fNRI model is smaller in size and significantly outperforms the original in both edge and trajectory prediction, establishing a new state-of-the-art. We also present a simplified variant of our model, which demonstrates the NRI's formulation as a variational auto-encoder is not necessary for good performance, and make an adaptation to the NRI's training routine, significantly improving its ability to model complex physical dynamical systems.