arXiv subjects

Charles Tapley Hoyt

Publications and source records attributed to Charles Tapley Hoyt.

At least 19 recordsLinked to original sources

arXiv2026

The Cell Ontology in the age of single-cell omics

Single-cell omics technologies have transformed our understanding of cellular diversity by enabling high-resolution profiling of individual cells. However, the unprecedented scale and heterogeneity of these datasets demand robust frameworks for data integration and annotation. The Cell Ontology (CL) has emerged as a pivotal resource for achieving FAIR (Findable, Accessible, Interoperable, and Reusable) data principles by providing standardized, species-agnostic terms for canonical cell types - forming a core component of a wide range of platforms and tools. In this paper, we describe the wide variety of uses of CL in these platforms and tools and detail ongoing work to improve and extend CL content including the addition of transcriptomic types, working closely with major atlasing efforts including the Human Cell Atlas and the Brain Initiative Cell Atlas Network to support their needs. We cover the challenges and future plans for harmonising classical and transcriptomic cell type definitions, integrating markers and using Large Language Models (LLMs) to improve content and efficiency of CL workflows.

q-bio.OT↗

arXiv2025

Teaching RDM in a smart advanced inorganic lab course and its provision in the DALIA platform

Research data management (RDM) is a key data literacy skill that chemistry students must acquire. Concepts such as the FAIR data principles (Findable, Accessible, Interoperable, Reusable) should be taught and applied in undergraduate studies already. Traditionally, research data from labs, theses, and internships were handwritten and stored in inaccessible formats such as PDFs, limiting reuse and machine learning applications. At RWTH Aachen University, a fifth-semester lab course introduces students to the electronic laboratory notebook (ELN) Chemotion, an open-source DFG-funded tool linked to the national NFDI4Chem initiative. Students plan, document, and evaluate experiments digitally, ensuring metadata and analysis are captured for long-term reuse. Chemotion's intuitive interface and repository enable sustainable data sharing. To reinforce RDM, students receive a seminar and access to online training videos with interactive Moodle elements. Herein we highlight the use of the DALIA platform as a discovery tool for the students.

cs.DB↗

arXiv2025

More Rigorous Software Engineering Would Improve Reproducibility in Machine Learning Research

While experimental reproduction remains a pillar of the scientific method, we observe that the software best practices supporting the reproduction of machine learning ( ML ) research are often undervalued or overlooked, leading both to poor reproducibility and damage to trust in the ML community. We quantify these concerns by surveying the usage of software best practices in software repositories associated with publications at major ML conferences and journals such as NeurIPS, ICML, ICLR, TMLR, and MLOSS within the last decade. We report the results of this survey that identify areas where software best practices are lacking and areas with potential for growth in the ML community. Finally, we discuss the implications and present concrete recommendations on how we, as a community, can improve reproducibility in ML research.

cs.SE↗

arXiv2025

Causal identification with $Y_0$

We present the $Y_0$ Python package, which implements causal identification algorithms that apply interventional, counterfactual, and transportability queries to data from (randomized) controlled trials, observational studies, or mixtures thereof. $Y_0$ focuses on the qualitative investigation of causation, helping researchers determine whether a causal relationship can be estimated from available data before attempting to estimate how strong that relationship is. Furthermore, $Y_0$ provides guidance on how to transform the causal query into a symbolic estimand that can be non-parametrically estimated from the available data. $Y_0$ provides a domain-specific language for representing causal queries and estimands as symbolic probabilistic expressions, tools for representing causal graphical models with unobserved confounders, such as acyclic directed mixed graphs (ADMGs), and implementations of numerous identification algorithms from the recent causal inference literature. The $Y_0$ source code can be found under the MIT License at https://github.com/y0-causal-inference/y0 and it can be installed with pip install y0.

cs.AI↗

arXiv2025

Improving reproducibility of cheminformatics workflows with chembl-downloader

Many modern cheminformatics workflows derive datasets from ChEMBL, but few of these datasets are published with accompanying code for their generation. Consequently, their methodologies (e.g., selection, filtering, aggregation) are opaque, reproduction is difficult, and interpretation of results therefore lacks important context. Further, such static datasets quickly become out-of-date. For example, the current version of ChEMBL is v35 (as of December 2024), but ExCAPE-DB uses v20, Deep Confidence uses v23, the consensus dataset from Isigkeit _et al._ (2022) uses v28, and Papyrus uses v30. Therefore, there is a need for tools that provide reproducible bulk access to the latest (or a given) version of ChEMBL in order to enable researchers to make their derived datasets more transparent, updatable, and trustworthy. This article introduces `chembl-downloader`, a Python package for the reproducible acquisition, access, and manipulation of ChEMBL data through its FTP server. It can be downloaded under the MIT license from https://github.com/cthoyt/chembl-downloader and installed from PyPI with `pip install chembl-downloader.`

q-bio.QM↗

arXiv2024

An Open-Source Knowledge Graph Ecosystem for the Life Sciences

Translational research requires data at multiple scales of biological organization. Advancements in sequencing and multi-omics technologies have increased the availability of these data, but researchers face significant integration challenges. Knowledge graphs (KGs) are used to model complex phenomena, and methods exist to construct them automatically. However, tackling complex biomedical integration problems requires flexibility in the way knowledge is modeled. Moreover, existing KG construction methods provide robust tooling at the cost of fixed or limited choices among knowledge representation models. PheKnowLator (Phenotype Knowledge Translator) is a semantic ecosystem for automating the FAIR (Findable, Accessible, Interoperable, and Reusable) construction of ontologically grounded KGs with fully customizable knowledge representation. The ecosystem includes KG construction resources (e.g., data preparation APIs), analysis tools (e.g., SPARQL endpoints and abstraction algorithms), and benchmarks (e.g., prebuilt KGs and embeddings). We evaluated the ecosystem by systematically comparing it to existing open-source KG construction methods and by analyzing its computational performance when used to construct 12 large-scale KGs. With flexible knowledge representation, PheKnowLator enables fully customizable KGs without compromising performance or usability.

cs.AI↗

arXiv2023

Democratising Knowledge Representation with BioCypher

Standardising the representation of biomedical knowledge among all researchers is an insurmountable task, hindering the effectiveness of many computational methods. To facilitate harmonisation and interoperability despite this fundamental challenge, we propose to standardise the framework of knowledge graph creation instead. We implement this standardisation in BioCypher, a FAIR (findable, accessible, interoperable, reusable) framework to transparently build biomedical knowledge graphs while preserving provenances of the source data. Mapping the knowledge onto biomedical ontologies helps to balance the needs for harmonisation, human and machine readability, and ease of use and accessibility to non-specialist researchers. We demonstrate the usefulness of this framework on a variety of use cases, from maintenance of task-specific knowledge stores, to interoperability between biomedical domains, to on-demand building of task-specific knowledge graphs for federated learning. BioCypher (https://biocypher.org) frees up valuable developer time; we encourage further development and usage by the community.

q-bio.MN↗

arXiv2022

Experimental design for causal query estimation in partially observed biomolecular networks

Estimating a causal query from observational data is an essential task in the analysis of biomolecular networks. Estimation takes as input a network topology, a query estimation method, and observational measurements on the network variables. However, estimations involving many variables can be experimentally expensive, and computationally intractable. Moreover, using the full set of variables can be detrimental, leading to bias, or increasing the variance in the estimation. Therefore, designing an experiment based on a well-chosen subset of network components can increase estimation accuracy, and reduce experimental and computational costs. We propose a simulation-based algorithm for selecting sub-networks that support unbiased estimators of the causal query under a constraint of cost, ranked with respect to the variance of the estimators. The simulations are constructed based on historical experimental data, or based on known properties of the biological system. Three case studies demonstrated the effectiveness of well-chosen network subsets for estimating causal queries from observational data. All the case studies are reproducible and available at https://github.com/srtaheri/Simplified_LVM.

q-bio.BM↗

arXiv2022

Do-calculus enables estimation of causal effects in partially observed biomolecular pathways

Estimating causal queries, such as changes in protein abundance in response to a perturbation, is a fundamental task in the analysis of biomolecular pathways. The estimation requires experimental measurements on the pathway components. However, in practice many pathway components are left unobserved (latent) because they are either unknown, or difficult to measure. Latent variable models (LVMs) are well-suited for such estimation. Unfortunately, LVM-based estimation of causal queries can be inaccurate when parameters of the latent variables are not uniquely identified, or when the number of latent variables is misspecified. This has limited the use of LVMs for causal inference in biomolecular pathways. In this manuscript, we propose a general and practical approach for LVM-based estimation of causal queries. We prove that, despite the challenges above, LVM-based estimators of causal queries are accurate if the queries are identifiable according to Pearl's do-calculus, and describe an algorithm for its estimation. We illustrate the breadth and the practical utility of this approach for estimating causal queries in four synthetic and two experimental case studies, where structures of biomolecular pathways challenge the existing methods for causal query estimation. The code and the data documenting all the case studies are available at \url{https://github.com/srtaheri/LVMwithDoCalculus}

cs.LG↗

arXiv2022

Ontology Development Kit: a toolkit for building, maintaining, and standardising biomedical ontologies

Similar to managing software packages, managing the ontology life cycle involves multiple complex workflows such as preparing releases, continuous quality control checking, and dependency management. To manage these processes, a diverse set of tools is required, from command line utilities to powerful ontology engineering environments such as ROBOT. Particularly in the biomedical domain, which has developed a set of highly diverse yet inter-dependent ontologies, standardising release practices and metadata, and establishing shared quality standards, are crucial to enable interoperability. The Ontology Development Kit (ODK) provides a set of standardised, customisable, and automatically executable workflows, and packages all required tooling in a single Docker image. In this paper, we provide an overview of how the ODK works, show how it is used in practice, and describe how we envision it driving standardisation efforts in our community.

cs.DB↗

arXiv2022

ChemicalX: A Deep Learning Library for Drug Pair Scoring

In this paper, we introduce ChemicalX, a PyTorch-based deep learning library designed for providing a range of state of the art models to solve the drug pair scoring task. The primary objective of the library is to make deep drug pair scoring models accessible to machine learning researchers and practitioners in a streamlined framework.The design of ChemicalX reuses existing high level model training utilities, geometric deep learning, and deep chemistry layers from the PyTorch ecosystem. Our system provides neural network layers, custom pair scoring architectures, data loaders, and batch iterators for end users. We showcase these features with example code snippets and case studies to highlight the characteristics of ChemicalX. A range of experiments on real world drug-drug interaction, polypharmacy side effect, and combination synergy prediction tasks demonstrate that the models available in ChemicalX are effective at solving the pair scoring task. Finally, we show that ChemicalX could be used to train and score machine learning models on large drug pair datasets with hundreds of thousands of compounds on commodity hardware.

cs.LG↗

arXiv2022

Understanding the Performance of Knowledge Graph Embeddings in Drug Discovery

Knowledge Graphs (KG) and associated Knowledge Graph Embedding (KGE) models have recently begun to be explored in the context of drug discovery and have the potential to assist in key challenges such as target identification. In the drug discovery domain, KGs can be employed as part of a process which can result in lab-based experiments being performed, or impact on other decisions, incurring significant time and financial costs and most importantly, ultimately influencing patient healthcare. For KGE models to have impact in this domain, a better understanding of not only of performance, but also the various factors which determine it, is required. In this study we investigate, over the course of many thousands of experiments, the predictive performance of five KGE models on two public drug discovery-oriented KGs. Our goal is not to focus on the best overall model or configuration, instead we take a deeper look at how performance can be affected by changes in the training setup, choice of hyperparameters, model parameter initialisation seed and different splits of the datasets. Our results highlight that these factors have significant impact on performance and can even affect the ranking of models. Indeed these factors should be reported along with model architectures to ensure complete reproducibility and fair comparisons of future work, and we argue this is critical for the acceptance of use, and impact of KGEs in a biomedical setting.

q-bio.BM↗

arXiv2022

A Unified Framework for Rank-based Evaluation Metrics for Link Prediction in Knowledge Graphs

The link prediction task on knowledge graphs without explicit negative triples in the training data motivates the usage of rank-based metrics. Here, we review existing rank-based metrics and propose desiderata for improved metrics to address lack of interpretability and comparability of existing metrics to datasets of different sizes and properties. We introduce a simple theoretical framework for rank-based metrics upon which we investigate two avenues for improvements to existing metrics via alternative aggregation functions and concepts from probability theory. We finally propose several new rank-based metrics that are more easily interpreted and compared accompanied by a demonstration of their usage in a benchmarking of knowledge graph embedding models.

cs.LG↗

arXiv2022

An Open Challenge for Inductive Link Prediction on Knowledge Graphs

An emerging trend in representation learning over knowledge graphs (KGs) moves beyond transductive link prediction tasks over a fixed set of known entities in favor of inductive tasks that imply training on one graph and performing inference over a new graph with unseen entities. In inductive setups, node features are often not available and training shallow entity embedding matrices is meaningless as they cannot be used at inference time with unseen entities. Despite the growing interest, there are not enough benchmarks for evaluating inductive representation learning methods. In this work, we introduce ILPC 2022, a novel open challenge on KG inductive link prediction. To this end, we constructed two new datasets based on Wikidata with various sizes of training and inference graphs that are much larger than existing inductive benchmarks. We also provide two strong baselines leveraging recently proposed inductive methods. We hope this challenge helps to streamline community efforts in the inductive graph representation learning area. ILPC 2022 follows best practices on evaluation fairness and reproducibility, and is available at https://github.com/pykeen/ilpc2022.

cs.LG↗

arXiv2021

A Review of Biomedical Datasets Relating to Drug Discovery: A Knowledge Graph Perspective

Drug discovery and development is a complex and costly process. Machine learning approaches are being investigated to help improve the effectiveness and speed of multiple stages of the drug discovery pipeline. Of these, those that use Knowledge Graphs (KG) have promise in many tasks, including drug repurposing, drug toxicity prediction and target gene-disease prioritisation. In a drug discovery KG, crucial elements including genes, diseases and drugs are represented as entities, whilst relationships between them indicate an interaction. However, to construct high-quality KGs, suitable data is required. In this review, we detail publicly available sources suitable for use in constructing drug discovery focused KGs. We aim to help guide machine learning and KG practitioners who are interested in applying new techniques to the drug discovery field, but who may be unfamiliar with the relevant data sources. The datasets are selected via strict criteria, categorised according to the primary type of information contained within and are considered based upon what information could be extracted to build a KG. We then present a comparative analysis of existing public drug discovery KGs and a evaluation of selected motivating case studies from the literature. Additionally, we raise numerous and unique challenges and issues associated with the domain and its datasets, whilst also highlighting key future research directions. We hope this review will motivate KGs use in solving key and emerging questions in the drug discovery domain.

cs.AI↗

arXiv2021

Bringing Light Into the Dark: A Large-scale Evaluation of Knowledge Graph Embedding Models Under a Unified Framework

The heterogeneity in recently published knowledge graph embedding models' implementations, training, and evaluation has made fair and thorough comparisons difficult. In order to assess the reproducibility of previously published results, we re-implemented and evaluated 21 interaction models in the PyKEEN software package. Here, we outline which results could be reproduced with their reported hyper-parameters, which could only be reproduced with alternate hyper-parameters, and which could not be reproduced at all as well as provide insight as to why this might be the case. We then performed a large-scale benchmarking on four datasets with several thousands of experiments and 24,804 GPU hours of computation time. We present insights gained as to best practices, best configurations for each model, and where improvements could be made over previously published best configurations. Our results highlight that the combination of model architecture, training approach, loss function, and the explicit modeling of inverse relations is crucial for a model's performances, and not only determined by the model architecture. We provide evidence that several architectures can obtain results competitive to the state-of-the-art when configured carefully. We have made all code, experimental configurations, results, and analyses that lead to our interpretations available at https://github.com/pykeen/pykeen and https://github.com/pykeen/benchmarking

cs.LG↗

arXiv2021

The role of metadata in reproducible computational research

Reproducible computational research (RCR) is the keystone of the scientific method for in silico analyses, packaging the transformation of raw data to published results. In addition to its role in research integrity, RCR has the capacity to significantly accelerate evaluation and reuse. This potential and wide-support for the FAIR principles have motivated interest in metadata standards supporting RCR. Metadata provides context and provenance to raw data and methods and is essential to both discovery and validation. Despite this shared connection with scientific data, few studies have explicitly described the relationship between metadata and RCR. This article employs a functional content analysis to identify metadata standards that support RCR functions across an analytic stack consisting of input data, tools, notebooks, pipelines, and publications. Our article provides background context, explores gaps, and discovers component trends of embeddedness and methodology weight from which we derive recommendations for future work.

cs.DL↗

arXiv2021

Leveraging Structured Biological Knowledge for Counterfactual Inference: a Case Study of Viral Pathogenesis

Counterfactual inference is a useful tool for comparing outcomes of interventions on complex systems. It requires us to represent the system in form of a structural causal model, complete with a causal diagram, probabilistic assumptions on exogenous variables, and functional assignments. Specifying such models can be extremely difficult in practice. The process requires substantial domain expertise, and does not scale easily to large systems, multiple systems, or novel system modifications. At the same time, many application domains, such as molecular biology, are rich in structured causal knowledge that is qualitative in nature. This manuscript proposes a general approach for querying a causal biological knowledge graph, and converting the qualitative result into a quantitative structural causal model that can learn from data to answer the question. We demonstrate the feasibility, accuracy and versatility of this approach using two case studies in systems biology. The first demonstrates the appropriateness of the underlying assumptions and the accuracy of the results. The second demonstrates the versatility of the approach by querying a knowledge base for the molecular determinants of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm, and performing counterfactual inference to estimate the causal effect of medical countermeasures for severely ill patients.

q-bio.QM↗