Machine learning framework to extract the biomarker potential of plasma IgG N-glycans towards disease risk stratification

Effective management of chronic diseases and cancer can greatly benefit from disease-specific biomarkers that enable informative screening and timely diagnosis. IgG N-glycans found in human plasma have the potential to be minimally invasive disease-specific biomarkers for all stages of disease development due to their plasticity in response to various genetic and environmental stimuli. Data analysis and machine learning (ML) approaches can assist in harnessing the potential of IgG glycomics towards biomarker discovery and the development of reliable predictive tools for disease screening. This study proposes an ML-based N-glycomic analysis framework that can be employed to build, optimise, and evaluate multiple ML pipelines to stratify patients based on disease risk in an interpretable manner. To design and test this framework, a published colorectal cancer (CRC) dataset from the Study of Colorectal Cancer in Scotland (SOCCS) cohort (1999-2006) was used. In particular, among the different pipelines tested, an XGBoost-based ML pipeline, which was tuned using multi-objective optimisation, calibrated using an inductive Venn-Abers predictor (IVAP), and evaluated via a nested cross-validation (NCV) scheme, achieved a mean area under the Receiver Operating Characteristic Curve (AUC-ROC) of 0.771 when classifying between age-, and sex-matched healthy controls and CRC patients. This performance suggests the potential of using the relative abundance of IgG N-glycans to define populations at elevated CRC risk who merit investigation or surveillance. Finally, the IgG N-glycans that highly impact CRC classification decisions were identified using a global model-agnostic interpretability technique, namely Accumulated Local Effects (ALE). We envision that open-source computational frameworks, such as the one presented herein, will be useful in supporting the translation of glycan-based biomarkers into clinical applications

Exploring parameter spaces with artificial intelligence and machine learning black-box optimisation algorithms

Constraining Beyond the Standard Model theories usually involves scanning highly multi-dimensional parameter spaces and check observable predictions against experimental bounds and theoretical constraints. Such task is often timely and computationally expensive, especially when the model is severely constrained and thus leading to very low random sampling efficiency. In this work we tackled this challenge using Artificial Intelligence and Machine Learning search algorithms used for Black-Box optimisation problems. Using the cMSSM and the pMSSM parameter spaces, we consider both the Higgs mass and the Dark Matter Relic Density constraints to study their sampling efficiency and parameter space coverage. We find our methodology to produce orders of magnitude improvement of sampling efficiency whilst reasonably covering the parameter space.We thank José Santiago Pérez and Jorge Romão for the careful reading of the paper draft and for the useful discussions. This work is supported by FCT - Fundação para a Ciência e a Tecnologia, I.P. under project CERN/FIS-PAR/0024/2019. FAS is also supported by FCT under the research grant with reference UI/BD/153105/2022. The computational work was partially done using the resources made available by RNCA and INCD under project CPCA/A1/401197/2021info:eu-repo/semantics/publishedVersio

Meta-learning algorithms and applications

Meta-learning in the broader context concerns how an agent learns about their own learning, allowing them to improve their learning process. Learning how to learn is not only beneficial for humans, but it has also shown vast benefits for improving how machines learn. In the context of machine learning, meta-learning enables models to improve their learning process by selecting suitable meta-parameters that influence the learning. For deep learning specifically, the meta-parameters typically describe details of the training of the model but can also include description of the model itself - the architecture. Meta-learning is usually done with specific goals in mind, for example trying to improve ability to generalize or learn new concepts from only a few examples. Meta-learning can be powerful, but it comes with a key downside: it is often computationally costly. If the costs would be alleviated, meta-learning could be more accessible to developers of new artificial intelligence models, allowing them to achieve greater goals or save resources. As a result, one key focus of our research is on significantly improving the efficiency of meta-learning. We develop two approaches: EvoGrad and PASHA, both of which significantly improve meta-learning efficiency in two common scenarios. EvoGrad allows us to efficiently optimize the value of a large number of differentiable meta-parameters, while PASHA enables us to efficiently optimize any type of meta-parameters but fewer in number. Meta-learning is a tool that can be applied to solve various problems. Most commonly it is applied for learning new concepts from only a small number of examples (few-shot learning), but other applications exist too. To showcase the practical impact that meta-learning can make in the context of neural networks, we use meta-learning as a novel solution for two selected problems: more accurate uncertainty quantification (calibration) and general-purpose few-shot learning. Both are practically important problems and using meta-learning approaches we can obtain better solutions than the ones obtained using existing approaches. Calibration is important for safety-critical applications of neural networks, while general-purpose few-shot learning tests model's ability to generalize few-shot learning abilities across diverse tasks such as recognition, segmentation and keypoint estimation. More efficient algorithms as well as novel applications enable the field of meta-learning to make more significant impact on the broader area of deep learning and potentially solve problems that were too challenging before. Ultimately both of them allow us to better utilize the opportunities that artificial intelligence presents