This Inaugural Lecture was given at Royal Holloway University of London in 1996. It covers an introduction to machine learning and describes various theoretical advances and practical projects in the field. The Lecture here is presented in its original format, but a few remarks have been added in 2025 to reflect recent developments, and the list of references has been updated to enhance the convenience and accuracy for readers. When did machine learning start? Maybe a good starting point is 1949, when Claude Shannon proposed a learning algorithm for chess-playing programs. Or maybe we should go back to the 1930s when Ronald Fisher developed discriminant analysis - a type of learning where the problem is to construct a decision rule that separates two types of vectors. Or could it be the 18th century when David Hume discussed the idea of induction? Or the 14th century, when William of Ockham formulated the principle of "simplicity" known as "Ockham's razor" (Ockham, by the way, is a small village not far from Royal Holloway). Or it may be that, like almost everything else in Western civilisation and culture, the origin of these ideas lies in the Mediterranean. After all, it was Aristotle who said that "we learn some things only by doing things". The field of machine learning has been greatly influenced by other disciplines and the subject is in itself not a very homogeneous discipline, but includes separate, overlapping subfields. There are many parallel lines of research in ML: inductive learning, neural networks, clustering, and theories of learning. They are all part of the more general field of machine learning.

Whole slide image (WSI) normalization remains a vital preprocessing step in computational pathology. Increasingly driven by deep learning, these models learn to approximate data distributions from training examples. This often results in outputs that gravitate toward the average, potentially masking diagnostically important features. More critically, they can introduce hallucinated content, artifacts that appear realistic but are not present in the original tissue, posing a serious threat to downstream analysis. These hallucinations are nearly impossible to detect visually, and current evaluation practices often overlook them. In this work, we demonstrate that the risk of hallucinations is real and underappreciated. While many methods perform adequately on public datasets, we observe a concerning frequency of hallucinations when these same models are retrained and evaluated on real-world clinical data. To address this, we propose a novel image comparison measure designed to automatically detect hallucinations in normalized outputs. Using this measure, we systematically evaluate several well-cited normalization methods retrained on real-world data, revealing significant inconsistencies and failures that are not captured by conventional metrics. Our findings underscore the need for more robust, interpretable normalization techniques and stricter validation protocols in clinical deployment.

Self-supervised learning (SSL) plays a central role in molecular representation learning. Yet, many recent innovations in masking-based pretraining are introduced as heuristics and lack principled evaluation, obscuring which design choices are genuinely effective. This work cast the entire pretrain-finetune workflow into a unified probabilistic framework, enabling a transparent comparison and deeper understanding of masking strategies. Building on this formalism, we conduct a controlled study of three core design dimensions: masking distribution, prediction target, and encoder architecture, under rigorously controlled settings. We further employ information-theoretic measures to assess the informativeness of pretraining signals and connect them to empirically benchmarked downstream performance. Our findings reveal a surprising insight: sophisticated masking distributions offer no consistent benefit over uniform sampling for common node-level prediction tasks. Instead, the choice of prediction target and its synergy with the encoder architecture are far more critical. Specifically, shifting to semantically richer targets yields substantial downstream improvements, particularly when paired with expressive Graph Transformer encoders. These insights offer practical guidance for developing more effective SSL methods for molecular graphs.

This paper proposes a novel self-supervised learning method for semantic segmentation using selective masking image reconstruction as the pretraining task. Our proposed method replaces the random masking augmentation used in most masked image modelling pretraining methods. The proposed selective masking method selectively masks image patches with the highest reconstruction loss by breaking the image reconstruction pretraining into iterative steps to leverage the trained model's knowledge. We show on two general datasets (Pascal VOC and Cityscapes) and two weed segmentation datasets (Nassar 2020 and Sugarbeets 2016) that our proposed selective masking method outperforms the traditional random masking method and supervised ImageNet pretraining on downstream segmentation accuracy by 2.9% for general datasets and 2.5% for weed segmentation datasets. Furthermore, we found that our selective masking method significantly improves accuracy for the lowest-performing classes. Lastly, we show that using the same pretraining and downstream dataset yields the best result for low-budget self-supervised pretraining. Our proposed Selective Masking Image Reconstruction method provides an effective and practical solution to improve end-to-end semantic segmentation workflows, especially for scenarios that require limited model capacity to meet inference speed and computational resource requirements.

Time series classification faces a fundamental trade-off between accuracy and computational efficiency. While comprehensive ensembles like HIVE-COTE 2.0 achieve state-of-the-art accuracy, their 340-hour training time on the UCR benchmark renders them impractical for large-scale datasets. We investigate whether targeted combinations of two efficient algorithms from complementary paradigms can capture ensemble benefits while maintaining computational feasibility. Combining Hydra (competing convolutional kernels) and Quant (hierarchical interval quantiles) across six ensemble configurations, we evaluate performance on 10 large-scale MONSTER datasets (7,898 to 1,168,774 training instances). Our strongest configuration improves mean accuracy from 0.829 to 0.836, succeeding on 7 of 10 datasets. However, prediction-combination ensembles capture only 11% of theoretical oracle potential, revealing a substantial meta-learning optimization gap. Feature-concatenation approaches exceeded oracle bounds by learning novel decision boundaries, while prediction-level complementarity shows moderate correlation with ensemble gains. The central finding: the challenge has shifted from ensuring algorithms are different to learning how to combine them effectively. Current meta-learning strategies struggle to exploit the complementarity that oracle analysis confirms exists. Improved combination strategies could potentially double or triple ensemble gains across diverse time series classification applications.

Influenza A viruses (IAVs) evolve antigenically at a pace that requires frequent vaccine updates, yet the haemagglutination inhibition (HI) assays used to quantify antigenicity are labor-intensive and unscalable. As a result, genomic data vastly outpace available phenotypic labels, limiting the effectiveness of traditional supervised models. We hypothesize that combining pre-trained Protein Language Models (PLMs) with Semi-Supervised Learning (SSL) can retain high predictive accuracy even when labeled data are scarce. We evaluated two SSL strategies, Self-training and Label Spreading, against fully supervised baselines using four PLM-derived embeddings (ESM-2, ProtVec, ProtT5, ProtBert) applied to haemagglutinin (HA) sequences. A nested cross-validation framework simulated low-label regimes (25%, 50%, 75%, and 100% label availability) across four IAV subtypes (H1N1, H3N2, H5N1, H9N2). SSL consistently improved performance under label scarcity. Self-training with ProtVec produced the largest relative gains, showing that SSL can compensate for lower-resolution representations. ESM-2 remained highly robust, achieving F1 scores above 0.82 with only 25% labeled data, indicating that its embeddings capture key antigenic determinants. While H1N1 and H9N2 were predicted with high accuracy, the hypervariable H3N2 subtype remained challenging, although SSL mitigated the performance decline. These findings demonstrate that integrating PLMs with SSL can address the antigenicity labeling bottleneck and enable more effective use of unlabeled surveillance sequences, supporting rapid variant prioritization and timely vaccine strain selection.

We propose Point-PNG, a novel self-supervised learning framework that generates conditional pseudo-negatives in the latent space to learn point cloud representations that are both discriminative and transformation-sensitive. Conventional self-supervised learning methods focus on achieving invariance, discarding transformation-specific information. Recent approaches incorporate transformation sensitivity by explicitly modeling relationships between original and transformed inputs. However, they often suffer from an invariant-collapse phenomenon, where the predictor degenerates into identity mappings, resulting in latent representations with limited variation across transformations. To address this, we propose Point-PNG that explicitly penalizes invariant collapse through pseudo-negatives generation, enabling the network to capture richer transformation cues while preserving discriminative representations. To this end, we introduce a parametric network, COnditional Pseudo-Negatives Embedding (COPE), which learns localized displacements induced by transformations within the latent space. A key challenge arises when jointly training COPE with the MAE, as it tends to converge to trivial identity mappings. To overcome this, we design a loss function based on pseudo-negatives conditioned on the transformation, which penalizes such trivial invariant solutions and enforces meaningful representation learning. We validate Point-PNG on shape classification and relative pose estimation tasks, showing competitive performance on ModelNet40 and ScanObjectNN under challenging evaluation protocols, and achieving superior accuracy in relative pose estimation compared to supervised baselines.

Semi-supervised multi-label learning (SSMLL) aims to address the challenge of limited labeled data in multi-label learning (MLL) by leveraging unlabeled data to improve the model's performance. While pseudo-labeling has become a dominant strategy in SSMLL, most existing methods assign equal weights to all pseudo-labels regardless of their quality, which can amplify the impact of noisy or uncertain predictions and degrade the overall performance. In this paper, we theoretically verify that the optimal weight for a pseudo-label should reflect its correctness likelihood. Empirically, we observe that on the same dataset, the correctness likelihood distribution of unlabeled data remains stable, even as the number of labeled training samples varies. Building on this insight, we propose Distribution-Calibrated Pseudo-labeling (DiCaP), a correctness-aware framework that estimates posterior precision to calibrate pseudo-label weights. We further introduce a dual-thresholding mechanism to separate confident and ambiguous regions: confident samples are pseudo-labeled and weighted accordingly, while ambiguous ones are explored by unsupervised contrastive learning. Experiments conducted on multiple benchmark datasets verify that our method achieves consistent improvements, surpassing state-of-the-art methods by up to 4.27%.

Covariate distribution shift occurs when certain structural features present in the test set are absent from the training set. It is a common type of out-of-distribution (OOD) problem, frequently encountered in real-world graph data with complex structures. Existing research has revealed that most out-of-the-box graph neural networks (GNNs) fail to account for covariate shifts. Furthermore, we observe that existing methods aimed at addressing covariate shifts often fail to fully leverage the rich information contained within the latent space. Motivated by the potential of the latent space, we introduce a new method called MPAIACL for More Powerful Adversarial Invariant Augmentation using Contrastive Learning. MPAIACL leverages contrastive learning to unlock the full potential of vector representations by harnessing their intrinsic information. Through extensive experiments, MPAIACL demonstrates its robust generalization and effectiveness, as it performs well compared with other baselines across various public OOD datasets. The code is publicly available at https://github.com/flzeng1/MPAIACL.

This study systematically compared data-driven and model-based strategies for metabolite quantification in magnetic resonance spectroscopy (MRS), focusing on resilience to out-of-distribution (OoD) effects and the balance between accuracy, robustness, and generalizability. A neural network designed for MRS quantification was trained using three distinct strategies: supervised regression, self-supervised learning, and test-time adaptation. These were compared against model-based fitting tools. Experiments combined large-scale simulated data, designed to probe metabolite concentration extrapolation and signal variability, with 1H single-voxel 7T in-vivo human brain spectra. In simulations, supervised learning achieved high accuracy for spectra similar to those in the training distribution, but showed marked degradation when extrapolated beyond the training distribution. Test-time adaptation proved more resilient to OoD effects, while self-supervised learning achieved intermediate performance. In-vivo experiments showed larger variance across the methods (data-driven and model-based) due to domain shift. Across all strategies, overlapping metabolites and baseline variability remained persistent challenges. While strong performance can be achieved by data-driven methods for MRS metabolite quantification, their reliability is contingent on careful consideration of the training distribution and potential OoD effects. When such conditions in the target distribution cannot be anticipated, test-time adaptation strategies ensure consistency between the quantification, the data, and the model, enabling reliable data-driven MRS pipelines.