Dónal Landers

Oskar Wysocki, Jessica Katharine Davies, Markel Vigo et al.

This paper contributes with a pragmatic evaluation framework for explainable Machine Learning (ML) models for clinical decision support. The study revealed a more nuanced role for ML explanation models, when these are pragmatically embedded in the clinical context. Despite the general positive attitude of healthcare professionals (HCPs) towards explanations as a safety and trust mechanism, for a significant set of participants there were negative effects associated with confirmation bias, accentuating model over-reliance and increased effort to interact with the model. Also, contradicting one of its main intended functions, standard explanatory models showed limited ability to support a critical understanding of the limitations of the model. However, we found new significant positive effects which repositions the role of explanations within a clinical context: these include reduction of automation bias, addressing ambiguous clinical cases (cases where HCPs were not certain about their decision) and support of less experienced HCPs in the acquisition of new domain knowledge.

Magdalena Wysocka, Oskar Wysocki, Marie Zufferey et al.

There is an increasing interest in the use of Deep Learning (DL) based methods as a supporting analytical framework in oncology. However, most direct applications of DL will deliver models with limited transparency and explainability, which constrain their deployment in biomedical settings. This systematic review discusses DL models used to support inference in cancer biology with a particular emphasis on multi-omics analysis. It focuses on how existing models address the need for better dialogue with prior knowledge, biological plausibility and interpretability, fundamental properties in the biomedical domain. For this, we retrieved and analyzed 42 studies focusing on emerging architectural and methodological advances, the encoding of biological domain knowledge and the integration of explainability methods. We discuss the recent evolutionary arch of DL models in the direction of integrating prior biological relational and network knowledge to support better generalisation (e.g. pathways or Protein-Protein-Interaction networks) and interpretability. This represents a fundamental functional shift towards models which can integrate mechanistic and statistical inference aspects. We introduce a concept of bio-centric interpretability and according to its taxonomy, we discuss representational methodologies for the integration of domain prior knowledge in such models. The paper provides a critical outlook into contemporary methods for explainability and interpretabiltiy used in DL for cancer. The analysis points in the direction of a convergence between encoding prior knowledge and improved interpretability. We introduce bio-centric interpretability which is an important step towards formalisation of biological interpretability of DL models and developing methods that are less problem- or application-specific.

Alex Bogatu, Zili Zhou, Dónal Landers et al.

Entailment trees have been proposed to simulate the human reasoning process of explanation generation in the context of open--domain textual question answering. However, in practice, manually constructing these explanation trees proves a laborious process that requires active human involvement. Given the complexity of capturing the line of reasoning from question to the answer or from claim to premises, the issue arises of how to assist the user in efficiently constructing multi--level entailment trees given a large set of available facts. In this paper, we frame the construction of entailment trees as a sequence of active premise selection steps, i.e., for each intermediate node in an explanation tree, the expert needs to annotate positive and negative examples of premise facts from a large candidate list. We then iteratively fine--tune pre--trained Transformer models with the resulting positive and tightly controlled negative samples and aim to balance the encoding of semantic relationships and explanatory entailment relationships. Experimental evaluation confirms the measurable efficiency gains of the proposed active fine--tuning method in facilitating entailment trees construction: up to 20\% improvement in explanatory premise selection when compared against several alternatives.

Oskar Wysocki, Zili Zhou, Paul O'Regan et al.

Specialised transformers-based models (such as BioBERT and BioMegatron) are adapted for the biomedical domain based on publicly available biomedical corpora. As such, they have the potential to encode large-scale biological knowledge. We investigate the encoding and representation of biological knowledge in these models, and its potential utility to support inference in cancer precision medicine - namely, the interpretation of the clinical significance of genomic alterations. We compare the performance of different transformer baselines; we use probing to determine the consistency of encodings for distinct entities; and we use clustering methods to compare and contrast the internal properties of the embeddings for genes, variants, drugs and diseases. We show that these models do indeed encode biological knowledge, although some of this is lost in fine-tuning for specific tasks. Finally, we analyse how the models behave with regard to biases and imbalances in the dataset.