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Ross D. King

Publications and source records attributed to Ross D. King.

At least 19 recordsLinked to original sources
arXiv2026

Hierarchy-Aware Semantic Losses for Knowledge Graph Link Prediction

Knowledge graphs are often accompanied by ontological class hierarchies that encode valuable semantic information, yet many link prediction methods either ignore such hierarchies or incorporate them indirectly through additional graph edges. Recent work introduced hierarchy-aware graph neural networks (GNNs), which use semantic losses derived from box embeddings to encourage satisfaction of subclass relationships during GNN-based representation learning. While this approach has shown promise for biological regression tasks, its effectiveness for knowledge graph link prediction has not been investigated. In this paper we evaluate hierarchy-aware semantic losses on link prediction across three benchmark datasets: AIFB, CoDEx, and BioKG. We combine graph neural network encoders with box-embedding-based semantic losses that encourage learned representations to better satisfy ontology-derived class hierarchies, and compare this approach to both standard link prediction models and models incorporating subclass relations as graph edges. Across all datasets, hierarchy-aware semantic losses significantly improve mean reciprocal rank (MRR) and consistently outperform models that incorporate hierarchy information through additional subclass edges. Relative to the baseline GNN models, MRR improved by 7.6%, 2.4%, and 15.5% on AIFB, CoDEx, and BioKG, respectively. Furthermore, semantic losses consistently outperform the alternative of augmenting the graph with subclass edges. These results are consistent with ontology-derived class hierarchies providing complementary information to graph structure, and suggest that encouraging hierarchical consistency through semantic losses is an effective and comparatively parameter-efficient mechanism for improving knowledge graph link prediction.

cs.LG↗
arXiv2026

The Past and Future of AI Scientists

We present a survey of the past and future of AI Scientists: machines capable of automating science. AI Scientists can originate hypotheses, deduce their consequences, design and execute experiments, interpret their results, and revise their beliefs. Such systems are integrated scientific agents, connected to the literature, formal knowledge, mathematical models, simulations, data-analysis systems and physical laboratories. Adam was the first machine to make novel scientific discoveries through cycles of hypothesis formation and physical experimentation. Eve established the architecture of the modern self-driving laboratory. Foundation models, autonomous agents and laboratory robotics now make it possible to build systems far more general than either Adam or Eve. The central problem is no longer whether individual components of science can be automated. They can. The problem is integration. AI Scientists must combine neural learning with logic, probability, mathematics, causal reasoning, simulation, experimental design, robotics and formal scientific records. AI Scientists have the potential to transform science: to make science faster, cheaper, more systematic and more reproducible. AI Scientists could investigate systems too complicated for unaided human science, and enable thousands of AI scientists to work together on single problems. The Nobel Turing Challenge sets the goal of developing by 2050 AI systems capable of automating Nobel-quality discoveries. Progress is ahead of schedule. When we succeed it will create a new form of science and transform the world.

cs.AI↗
arXiv2026

Iterative AI-guided optimisation of selective triple-drug combinations for breast cancer

Personalised cancer therapy aims to tailor treatment to individual tumour profiles, yet tumour heterogeneity and adaptive resistance continue to limit clinical efficacy. Drug combinations offer a strategy to overcome resistance by simultaneously targeting multiple pathways, but their rational design is constrained by the vast combinatorial search space and experimental cost. Here, we present an AI-guided, QSAR-driven iterative optimisation framework that integrates machine learning with automated experimental screening to enable closed-loop discovery of selective multi-drug therapies. Starting from an initial random screen, the system iteratively predicts, tests, and refines three-drug combinations targeting MCF7 breast cancer cells. Incorporation of non-tumorigenic MCF10A cells enables explicit optimisation of tumour-selective efficacy, prioritising regimens that maximise cancer cell killing while sparing healthy cells. Across successive iterations, the framework rapidly enriched for highly selective, high-efficacy combinations, while maintaining chemical and mechanistic diversity and avoiding convergence on a narrow solution space. By continuously learning from experimental feedback, the approach efficiently navigates millions of combinations to identify a small set of validated, tumour-selective regimens. These results establish a scalable proof-of-concept for AI-driven, closed-loop optimisation of higher-order drug combinations, demonstrating how iterative integration of computation and experimentation can enable adaptive and potentially personalised therapeutic design in precision oncology.

q-bio.QM↗
arXiv2026

A sensitivity-based method for bilevel optimization problems: Theoretical analysis and computational performance

Bilevel optimization provides a powerful framework for modelling hierarchical decision-making systems. This work presents a sensitivity-based algorithm that addresses the bilevel structure directly by treating the lower-level optimal solution as an implicit, locally differentiable function of the upper-level variables, thereby avoiding classical single-level reformulations. Under standard regularity assumptions on the lower level, an adjoint-based representation of the reduced upper-level gradient is derived, replacing explicit construction of the sensitivity Jacobian with a single linear adjoint solve per iteration and reducing gradient evaluation cost by a factor equal to the upper-level dimension. The reduced problem is solved within an Augmented Lagrangian framework, with inner subproblems managed by an L-BFGS-B quasi-Newton solver. Convergence to KKT points of the reduced problem is established, and these points are shown to be equivalent to S-stationary solutions of the associated mathematical programme with complementarity constraints under MPEC-LICQ. Computational experiments on benchmark bilevel problems validate the method's correctness and robustness, and demonstrate the effectiveness of a pragmatic dual-criterion stopping condition in handling the asymmetric primal-dual convergence rates characteristic of augmented Lagrangian methods.

math.OC↗
arXiv2026

Graph Neural Network based Hierarchy-Aware Embeddings of Knowledge Graphs: Applications to Yeast Phenotype Prediction

We present a method for finding hierarchy-aware embeddings of knowledge graphs (KGs) using graph neural networks (GNNs) enriched with a semantic loss derived from underlying ontologies. This method yields embeddings that better reflect domain knowledge. To demonstrate their utility, we predict and interpret the effects of gene deletions in the yeast Saccharomyces cerevisiae and learn box embeddings for KGs in the absence of a prediction task. We further show how box embeddings can serve as the basis for evaluating KG revisions. Our yeast KG is constructed from community databases and ontology terms. Low-dimensional box embeddings combined with GNNs are used to predict cell growth for double gene knockouts. Over 10-fold cross validation, these predictions have a mean $R^2$~score~of~0.360, significantly higher than baseline comparisons, demonstrating that high-level qualitative knowledge is informative about experimental outcomes. Incorporating semantic loss terms in the training of the models improves their predictive performance ($R^2$=0.377) by aligning embeddings with ontology structure. This shows that class hierarchies from ontologies can be exploited for quantitative prediction. We also test the trained models on triple gene knockouts, showing they generalise to data beyond those seen in training. Additionally, by identifying co-occurring relations in the yeast KG important for the cell-growth predictions, we construct hypotheses about interacting traits in yeast. A biological experiment validates one such finding, revealing an association between inositol utilisation and osmotic stress resistance, highlighting the model's potential to guide biological discovery.

cs.LG↗
arXiv2026

The Use of AI-Robotic Systems for Scientific Discovery

The process of developing theories and models and testing them with experiments is fundamental to the scientific method. Automating the entire scientific method then requires not only automation of the induction of theories from data, but also experimentation from design to implementation. This is the idea behind a robot scientist -- a coupled system of AI and laboratory robotics that has agency to test hypotheses with real-world experiments. In this chapter we explore some of the fundamentals of robot scientists in the philosophy of science. We also map the activities of a robot scientist to machine learning paradigms, and argue that the scientific method shares an analogy with active learning. We demonstrate these concepts using examples from previous robot scientists, and also from Genesis: a next generation robot scientist designed for research in systems biology, comprising a micro-fluidic system with 1000 computer-controlled micro-bioreactors and interpretable models based in controlled vocabularies and logic.

cs.LG↗
arXiv2026

Learning Logical Rules using Minimum Message Length

Unifying probabilistic and logical learning is a key challenge in AI. We introduce a Bayesian inductive logic programming approach that learns minimum message length hypotheses from noisy data. Our approach balances hypothesis complexity and data fit through priors, which favour more general programs, and a likelihood, which favours accurate programs. Our experiments on several domains, including game playing and drug design, show that our method significantly outperforms previous methods, notably those that learn minimum description length programs. Our results also show that our approach is data-efficient and insensitive to example balance, including the ability to learn from exclusively positive examples.

cs.AI↗
arXiv2025

Mitigating Hallucinations in Zero-Shot Scientific Summarisation: A Pilot Study

Large language models (LLMs) produce context inconsistency hallucinations, which are LLM generated outputs that are misaligned with the user prompt. This research project investigates whether prompt engineering (PE) methods can mitigate context inconsistency hallucinations in zero-shot LLM summarisation of scientific texts, where zero-shot indicates that the LLM relies purely on its pre-training data. Across eight yeast biotechnology research paper abstracts, six instruction-tuned LLMs were prompted with seven methods: a baseline prompt, two levels of increasing instruction complexity (PE-1 and PE-2), two levels of context repetition (CR-K1 and CR-K2), and two levels of random addition (RA-K1 and RA-K2). Context repetition involved the identification and repetition of K key sentences from the abstract, whereas random addition involved the repetition of K randomly selected sentences from the abstract, where K is 1 or 2. A total of 336 LLM-generated summaries were evaluated using six metrics: ROUGE-1, ROUGE-2, ROUGE-L, BERTScore, METEOR, and cosine similarity, which were used to compute the lexical and semantic alignment between the summaries and the abstracts. Four hypotheses on the effects of prompt methods on summary alignment with the reference text were tested. Statistical analysis on 3744 collected datapoints was performed using bias-corrected and accelerated (BCa) bootstrap confidence intervals and Wilcoxon signed-rank tests with Bonferroni-Holm correction. The results demonstrated that CR and RA significantly improve the lexical alignment of LLM-generated summaries with the abstracts. These findings indicate that prompt engineering has the potential to impact hallucinations in zero-shot scientific summarisation tasks.

cs.CL↗
arXiv2025

Compressing Chemistry Reveals Functional Groups

We introduce the first formal large-scale assessment of the utility of traditional chemical functional groups as used in chemical explanations. Our assessment employs a fundamental principle from computational learning theory: a good explanation of data should also compress the data. We introduce an unsupervised learning algorithm based on the Minimum Message Length (MML) principle that searches for substructures that compress around three million biologically relevant molecules. We demonstrate that the discovered substructures contain most human-curated functional groups as well as novel larger patterns with more specific functions. We also run our algorithm on 24 specific bioactivity prediction datasets to discover dataset-specific functional groups. Fingerprints constructed from dataset-specific functional groups are shown to significantly outperform other fingerprint representations, including the MACCS and Morgan fingerprint, when training ridge regression models on bioactivity regression tasks.

cs.LG↗
arXiv2025

Advancing Drug Development Through Strategic Cell Line and Compound Selection Using Drug Response Profiles

Early identification of sensitive cancer cell lines is essential for accelerating biomarker discovery and elucidating drug mechanism of action. Given the efficiency and low cost of small-scale drug screens relative to extensive omics profiling, we compared drug-response panel (DRP) descriptors against omics features for predictive capacity using gradient boosting tree models across the GDSC and CCLE drug response datasets. DRP descriptors consistently outperformed omics data across key performance metrics, with variable performance across different drugs. Using complementary explainability approaches, we confirmed known MAPK-inhibitor sensitivity signatures, and identified novel potential biomarker candidates for MEK1/2 and BTK/MNK inhibitors. Lastly, to demonstrate the utility of this approach in distinguishing phenotypes, we applied our models to the breast cancer line MCF7 versus the non-tumorigenic MCF10A, and successfully identified compounds that selectively inhibit MCF7 while sparing the non-tumorigenic MCF10A. This methodology, developed using focused drug and cell line panels, supports early-stage drug development by facilitating rational cell line selection and compound prioritisation, enabling more efficient biomarker identification and candidate assessment.

q-bio.QM↗
arXiv2025

Scientific Hypothesis Generation by a Large Language Model: Laboratory Validation in Breast Cancer Treatment

Large language models LLMs have transformed AI and achieved breakthrough performance on a wide range of tasks In science the most interesting application of LLMs is for hypothesis formation A feature of LLMs which results from their probabilistic structure is that the output text is not necessarily a valid inference from the training text These are termed hallucinations and are harmful in many applications In science some hallucinations may be useful novel hypotheses whose validity may be tested by laboratory experiments Here we experimentally test the application of LLMs as a source of scientific hypotheses using the domain of breast cancer treatment We applied the LLM GPT4 to hypothesize novel synergistic pairs of FDA-approved noncancer drugs that target the MCF7 breast cancer cell line relative to the nontumorigenic breast cell line MCF10A In the first round of laboratory experiments GPT4 succeeded in discovering three drug combinations out of twelve tested with synergy scores above the positive controls GPT4 then generated new combinations based on its initial results this generated three more combinations with positive synergy scores out of four tested We conclude that LLMs are a valuable source of scientific hypotheses.

q-bio.QM↗
arXiv2024

Genesis: Towards the Automation of Systems Biology Research

The cutting edge of applying AI to science is the closed-loop automation of scientific research: robot scientists. We have previously developed two robot scientists: `Adam' (for yeast functional biology), and `Eve' (for early-stage drug design)). We are now developing a next generation robot scientist Genesis. With Genesis we aim to demonstrate that an area of science can be investigated using robot scientists unambiguously faster, and at lower cost, than with human scientists. Here we report progress on the Genesis project. Genesis is designed to automatically improve system biology models with thousands of interacting causal components. When complete Genesis will be able to initiate and execute in parallel one thousand hypothesis-led closed-loop cycles of experiment per-day. Here we describe the core Genesis hardware: the one thousand computer-controlled $μ$-bioreactors. For the integrated Mass Spectrometry platform we have developed AutonoMS, a system to automatically run, process, and analyse high-throughput experiments. We have also developed Genesis-DB, a database system designed to enable software agents access to large quantities of structured domain information. We have developed RIMBO (Revisions for Improvements of Models in Biology Ontology) to describe the planned hundreds of thousands of changes to the models. We have demonstrated the utility of this infrastructure by developed two relational learning bioinformatic projects. Finally, we describe LGEM+ a relational learning system for the automated abductive improvement of genome-scale metabolic models.

cs.AI↗
arXiv2024

Automating the Practice of Science -- Opportunities, Challenges, and Implications

Automation transformed various aspects of our human civilization, revolutionizing industries and streamlining processes. In the domain of scientific inquiry, automated approaches emerged as powerful tools, holding promise for accelerating discovery, enhancing reproducibility, and overcoming the traditional impediments to scientific progress. This article evaluates the scope of automation within scientific practice and assesses recent approaches. Furthermore, it discusses different perspectives to the following questions: Where do the greatest opportunities lie for automation in scientific practice?; What are the current bottlenecks of automating scientific practice?; and What are significant ethical and practical consequences of automating scientific practice? By discussing the motivations behind automated science, analyzing the hurdles encountered, and examining its implications, this article invites researchers, policymakers, and stakeholders to navigate the rapidly evolving frontier of automated scientific practice.

cs.CY↗
arXiv2024

Personalised Medicine: Establishing predictive machine learning models for drug responses in patient derived cell culture

The concept of personalised medicine in cancer therapy is becoming increasingly important. There already exist drugs administered specifically for patients with tumours presenting well-defined mutations. However, the field is still in its infancy, and personalised treatments are far from being standard of care. Personalised medicine is often associated with the utilisation of omics data. Yet, implementation of multi-omics data has proven difficult, due to the variety and scale of the information within the data, as well as the complexity behind the myriad of interactions taking place within the cell. An alternative approach to precision medicine is to employ a function-based profile of the cell. This involves screening a range of drugs against patient derived cells. Here we demonstrate a proof-of-concept, where a collection of drug screens against a highly diverse set of patient-derived cell lines, are leveraged to identify putative treatment options for a 'new patient'. We show that this methodology is highly efficient in ranking the drugs according to their activity towards the target cells. We argue that this approach offers great potential, as activities can be efficiently imputed from various subsets of the drug treated cell lines that do not necessarily originate from the same tissue type.

q-bio.BM↗
arXiv2023

Extension of Transformational Machine Learning: Classification Problems

This study explores the application and performance of Transformational Machine Learning (TML) in drug discovery. TML, a meta learning algorithm, excels in exploiting common attributes across various domains, thus developing composite models that outperform conventional models. The drug discovery process, which is complex and time-consuming, can benefit greatly from the enhanced prediction accuracy, improved interpretability and greater generalizability provided by TML. We explore the efficacy of different machine learning classifiers, where no individual classifier exhibits distinct superiority, leading to the consideration of ensemble classifiers such as the Random Forest. Our findings show that TML outperforms base Machine Learning (ML) as the number of training datasets increases, due to its capacity to better approximate the correct hypothesis, overcome local optima, and expand the space of representable functions by combining separate classifiers capabilities. However, this superiority is relative to the resampling methods applied, with Near Miss demonstrating poorer performance due to noisy data, overlapping classes, and nonlinear class boundaries. Conversely, Random Over Sampling (ROS) provides a more robust performance given its resistance to noise and outliers, improved class overlap management, and suitability for nonlinear class boundaries.

q-bio.BM↗
arXiv2023

LGEM$^\text{+}$: a first-order logic framework for automated improvement of metabolic network models through abduction

Scientific discovery in biology is difficult due to the complexity of the systems involved and the expense of obtaining high quality experimental data. Automated techniques are a promising way to make scientific discoveries at the scale and pace required to model large biological systems. A key problem for 21st century biology is to build a computational model of the eukaryotic cell. The yeast Saccharomyces cerevisiae is the best understood eukaryote, and genome-scale metabolic models (GEMs) are rich sources of background knowledge that we can use as a basis for automated inference and investigation. We present LGEM+, a system for automated abductive improvement of GEMs consisting of: a compartmentalised first-order logic framework for describing biochemical pathways (using curated GEMs as the expert knowledge source); and a two-stage hypothesis abduction procedure. We demonstrate that deductive inference on logical theories created using LGEM+, using the automated theorem prover iProver, can predict growth/no-growth of S. cerevisiae strains in minimal media. LGEM+ proposed 2094 unique candidate hypotheses for model improvement. We assess the value of the generated hypotheses using two criteria: (a) genome-wide single-gene essentiality prediction, and (b) constraint of flux-balance analysis (FBA) simulations. For (b) we developed an algorithm to integrate FBA with the logic model. We rank and filter the hypotheses using these assessments. We intend to test these hypotheses using the robot scientist Genesis, which is based around chemostat cultivation and high-throughput metabolomics.

q-bio.QM↗
arXiv2023

Beating the Best: Improving on AlphaFold2 at Protein Structure Prediction

The goal of Protein Structure Prediction (PSP) problem is to predict a protein's 3D structure (confirmation) from its amino acid sequence. The problem has been a 'holy grail' of science since the Noble prize-winning work of Anfinsen demonstrated that protein conformation was determined by sequence. A recent and important step towards this goal was the development of AlphaFold2, currently the best PSP method. AlphaFold2 is probably the highest profile application of AI to science. Both AlphaFold2 and RoseTTAFold (another impressive PSP method) have been published and placed in the public domain (code & models). Stacking is a form of ensemble machine learning ML in which multiple baseline models are first learnt, then a meta-model is learnt using the outputs of the baseline level model to form a model that outperforms the base models. Stacking has been successful in many applications. We developed the ARStack PSP method by stacking AlphaFold2 and RoseTTAFold. ARStack significantly outperforms AlphaFold2. We rigorously demonstrate this using two sets of non-homologous proteins, and a test set of protein structures published after that of AlphaFold2 and RoseTTAFold. As more high quality prediction methods are published it is likely that ensemble methods will increasingly outperform any single method.

q-bio.BM↗
arXiv2018

Transformative Machine Learning

The key to success in machine learning (ML) is the use of effective data representations. Traditionally, data representations were hand-crafted. Recently it has been demonstrated that, given sufficient data, deep neural networks can learn effective implicit representations from simple input representations. However, for most scientific problems, the use of deep learning is not appropriate as the amount of available data is limited, and/or the output models must be explainable. Nevertheless, many scientific problems do have significant amounts of data available on related tasks, which makes them amenable to multi-task learning, i.e. learning many related problems simultaneously. Here we propose a novel and general representation learning approach for multi-task learning that works successfully with small amounts of data. The fundamental new idea is to transform an input intrinsic data representation (i.e., handcrafted features), to an extrinsic representation based on what a pre-trained set of models predict about the examples. This transformation has the dual advantages of producing significantly more accurate predictions, and providing explainable models. To demonstrate the utility of this transformative learning approach, we have applied it to three real-world scientific problems: drug-design (quantitative structure activity relationship learning), predicting human gene expression (across different tissue types and drug treatments), and meta-learning for machine learning (predicting which machine learning methods work best for a given problem). In all three problems, transformative machine learning significantly outperforms the best intrinsic representation.

cs.LG↗