ORCID Profile
0000-0003-1739-9882
Current Organisations
University of California, San Diego
,
Leeds Beckett University
,
Leeds Beckett University Leeds Business School
,
University of Bolton
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Publisher: Frontiers Media SA
Date: 21-01-2022
DOI: 10.3389/FPUBH.2021.831404
Abstract: The proliferation of wearable sensors that record physiological signals has resulted in an exponential growth of data on digital health. To select the appropriate repository for the increasing amount of collected data, intelligent procedures are becoming increasingly necessary. However, allocating storage space is a nuanced process. Generally, patients have some input in choosing which repository to use, although they are not always responsible for this decision. Patients are likely to have idiosyncratic storage preferences based on their unique circumstances. The purpose of the current study is to develop a new predictive model of health data storage to meet the needs of patients while ensuring rapid storage decisions, even when data is streaming from wearable devices. To create the machine learning classifier, we used a training set synthesized from small s les of experts who exhibited correlations between health data and storage features. The results confirm the validity of the machine learning methodology.
Publisher: Cold Spring Harbor Laboratory
Date: 11-09-2020
DOI: 10.1101/2020.09.11.290486
Abstract: Orphan G protein-coupled receptors (GPCRs) are largely intractable therapeutic targets, owing to the lack of chemical tools for exploring their pharmacology. The discovery of such tools, however, is h ered by a number of unknowns, such as effector coupling and appropriate positive controls. In our 2017 Nature Chemical Biology paper 1 , we developed a computational chemical tool discovery approach called GPCR Contact-Informed Neighboring Pocket (GPCR-CoINPocket). This method predicted pharmacological similarity of GPCRs in a ligand- and structure-independent manner, to enable the discovery of off-target activities of known compounds at orphan GPCRs and hence the identification of so-called surrogate ligands. Our orphan GPCR target for prospective surrogate ligand discovery efforts was GPR37L1, a brain-specific receptor linked to cerebellar development 2 and seizures 3 . We had previously demonstrated that GPR37L1 constitutively coupled to Gαs and generated ligand-independent increases in intracellular cAMP 4§ . Thus, the inverse agonist activities of computationally predicted surrogates were tested in the cAMP response element luciferase (CRE-luc) reporter gene assay in human embryonic kidney (HEK293) cells expressing either vector control or what we thought was untagged GPR37L1 in pcDNA3.1. However, we recently discovered that the GPR37L1 construct used in that study was incorrect: instead of pcDNA3.1, it carried the receptor inserted backwards into a yeast p426GPD vector (hereafter referred to as p426-r37L1). Here, we correct the cloning error and describe our subsequent unsuccessful efforts to re-test the computationally predicted GPR37L1 ligands (triggering an author-initiated retraction of 1 ). We, the authors, are working with the Nature Chemical Biology Editors to retract our 2017 paper ‘Orphan receptor ligand discovery by pickpocketing pharmacological neighbors’ 1 . The present manuscript is under review at Nature Chemical Biology as a Matters Arising accompaniment to the anticipated author-initiated retraction. We initiated the steps towards the retraction upon discovering a regrettable cloning error that put into question the in vitro findings reported in 1 . This action was unanimously agreed upon by all authors. The computational aspects of the original manuscript 1 are unaffected by this error.
Publisher: Wiley
Date: 05-03-2016
DOI: 10.1111/BPH.13452
Publisher: Springer Science and Business Media LLC
Date: 19-12-2016
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Paul Hollins.