Algebraic Shortcuts for Leave-One-Out Cross-Validation in Supervised Network Inference

AbstractMotivationSupervised machine learning techniques have traditionally been very successful at reconstructing biological networks, such as protein-ligand interaction, protein-protein interaction and gene regulatory networks. Recently, much emphasis has been placed on the correct evaluation of such supervised models. It is vital to distinguish between using the model to either predict new interactions in a given network or to predict interactions for a new vertex not present in the original network. Specific cross-validation schemes need to be used to assess the performance in such different prediction settings.ResultsWe present a series of leave-one-out cross-validation shortcuts to rapidly estimate the performance of state-of-the-art kernel-based network inference techniques.AvailabilityThe machine learning techniques with the algebraic shortcuts are implemented in the RLScore software package.

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Machine Learning for Causal Inference in Biological Networks: Perspectives of This Challenge

Frontiers in Bioinformatics ◽

10.3389/fbinf.2021.746712 ◽

2021 ◽

Vol 1 ◽

Author(s):

Paola Lecca

Keyword(s):

Machine Learning ◽

Biological Networks ◽

Network Inference ◽

Machine Learning Techniques ◽

Causal Relationships ◽

Learning Methods ◽

Machine Learning Methods ◽

Learning Techniques ◽

Physical Scale ◽

Computer Science Research

Most machine learning-based methods predict outcomes rather than understanding causality. Machine learning methods have been proved to be efficient in finding correlations in data, but unskilful to determine causation. This issue severely limits the applicability of machine learning methods to infer the causal relationships between the entities of a biological network, and more in general of any dynamical system, such as medical intervention strategies and clinical outcomes system, that is representable as a network. From the perspective of those who want to use the results of network inference not only to understand the mechanisms underlying the dynamics, but also to understand how the network reacts to external stimuli (e. g. environmental factors, therapeutic treatments), tools that can understand the causal relationships between data are highly demanded. Given the increasing popularity of machine learning techniques in computational biology and the recent literature proposing the use of machine learning techniques for the inference of biological networks, we would like to present the challenges that mathematics and computer science research faces in generalising machine learning to an approach capable of understanding causal relationships, and the prospects that achieving this will open up for the medical application domains of systems biology, the main paradigm of which is precisely network biology at any physical scale.

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Application of Machine Learning Techniques to Predict Binding Affinity for Drug Targets: A Study of Cyclin-Dependent Kinase 2

Current Medicinal Chemistry ◽

10.2174/2213275912666191102162959 ◽

2020 ◽

Vol 28 (2) ◽

pp. 253-265 ◽

Cited By ~ 3

Author(s):

Gabriela Bitencourt-Ferreira ◽

Amauri Duarte da Silva ◽

Walter Filgueira de Azevedo

Keyword(s):

Machine Learning ◽

Binding Affinity ◽

Predictive Performance ◽

Supervised Machine Learning ◽

Machine Learning Techniques ◽

Scoring Functions ◽

Cyclin Dependent Kinase ◽

Learning Models ◽

Learning Techniques ◽

Machine Learning Models

Background: The elucidation of the structure of cyclin-dependent kinase 2 (CDK2) made it possible to develop targeted scoring functions for virtual screening aimed to identify new inhibitors for this enzyme. CDK2 is a protein target for the development of drugs intended to modulate cellcycle progression and control. Such drugs have potential anticancer activities. Objective: Our goal here is to review recent applications of machine learning methods to predict ligand- binding affinity for protein targets. To assess the predictive performance of classical scoring functions and targeted scoring functions, we focused our analysis on CDK2 structures. Methods: We have experimental structural data for hundreds of binary complexes of CDK2 with different ligands, many of them with inhibition constant information. We investigate here computational methods to calculate the binding affinity of CDK2 through classical scoring functions and machine- learning models. Results: Analysis of the predictive performance of classical scoring functions available in docking programs such as Molegro Virtual Docker, AutoDock4, and Autodock Vina indicated that these methods failed to predict binding affinity with significant correlation with experimental data. Targeted scoring functions developed through supervised machine learning techniques showed a significant correlation with experimental data. Conclusion: Here, we described the application of supervised machine learning techniques to generate a scoring function to predict binding affinity. Machine learning models showed superior predictive performance when compared with classical scoring functions. Analysis of the computational models obtained through machine learning could capture essential structural features responsible for binding affinity against CDK2.

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Local mortality estimates during the COVID-19 pandemic in Italy

Journal of Population Economics ◽

10.1007/s00148-021-00857-y ◽

2021 ◽

Author(s):

Augusto Cerqua ◽

Roberta Di Stefano ◽

Marco Letta ◽

Sara Miccoli

Keyword(s):

Machine Learning ◽

Excess Mortality ◽

Control Method ◽

Local Level ◽

Supervised Machine Learning ◽

Machine Learning Techniques ◽

Mortality Data ◽

Official Method ◽

Learning Techniques ◽

Mortality Estimates

AbstractEstimates of the real death toll of the COVID-19 pandemic have proven to be problematic in many countries, Italy being no exception. Mortality estimates at the local level are even more uncertain as they require stringent conditions, such as granularity and accuracy of the data at hand, which are rarely met. The “official” approach adopted by public institutions to estimate the “excess mortality” during the pandemic draws on a comparison between observed all-cause mortality data for 2020 and averages of mortality figures in the past years for the same period. In this paper, we apply the recently developed machine learning control method to build a more realistic counterfactual scenario of mortality in the absence of COVID-19. We demonstrate that supervised machine learning techniques outperform the official method by substantially improving the prediction accuracy of the local mortality in “ordinary” years, especially in small- and medium-sized municipalities. We then apply the best-performing algorithms to derive estimates of local excess mortality for the period between February and September 2020. Such estimates allow us to provide insights about the demographic evolution of the first wave of the pandemic throughout the country. To help improve diagnostic and monitoring efforts, our dataset is freely available to the research community.

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