The NESHIE and CP Genetics Resource (NCGR): A database of genes and variants reported in neonatal encephalopathy with suspected hypoxic ischemic encephalopathy (NESHIE) and consequential cerebral palsy (CP)

Holborn, Megan A.; Ford, Graeme R.; Turner, Sarah; Mellet, Juanita; Van Rensburg, Jeanne; Joubert, Fourie; Pepper, Michael Sean

The NESHIE and CP Genetics Resource (NCGR): A database of genes and variants reported in neonatal encephalopathy with suspected hypoxic ischemic encephalopathy (NESHIE) and consequential cerebral palsy (CP)

Holborn, Megan A.; Ford, Graeme R.; Turner, Sarah; Mellet, Juanita; Van Rensburg, Jeanne; Joubert, Fourie; Pepper, Michael Sean

URI: http://hdl.handle.net/2263/90371

Date: 2022-11

Abstract:

Neonatal encephalopathy (NE) with suspected hypoxic ischaemic encephalopathy (HIE) (NESHIE) is a complex syndrome occurring in newborns, characterised by altered neurological function. It has been suggested that genetic variants may influence NESHIE susceptibility and outcomes. Unlike NESHIE, for which a limited number of genetic studies have been performed, many studies have identified genetic variants associated with cerebral palsy (CP), which can develop from severe NESHIE. Identifying variants in patients with CP, as a consequence of NESHIE, may provide a starting point for the identification of genetic variants associated with NESHIE outcomes. We have constructed NCGR (NESHIE and CP Genetics Resource), a database of genes and variants reported in patients with NESHIE and CP (where relevant to NESHIE), for the purpose of collating and comparing genetic findings between the two conditions. In this paper we describe the construction and functionality of NCGR. Furthermore, we demonstrate how NCGR can be used to prioritise genes and variants of potential clinical relevance that may underlie a genetic predisposition to NESHIE and contribute to an understanding of its pathogenesis.

Description:

DATA AVAILABILTY : All data generated or analysed during this study are included in this published article, supplementary information files, and the NCGR database repository. Access to the NCGR database is available at http://ncgr.bi.up.ac.za/. Additional data will be made available on request.

SUPPLEMENTARY DATA : SUPPLEMENTARY FIG. 1. User input for a complex query generated using NCGR's filter functionality to prioritise genes likely to predispose individuals to NESHIE. Abbreviations: CP: cerebral palsy; NESHIE: neonatal encephalopathy with suspected hypoxic ischemic encephalopathy; HPO: human phenotype ontology; NCGR: NESHIE and CP genetics resource.

SUPPLEMENTARY FIG. 2. Protein-protein interaction network constructed using genes that were prioritised based on evidence of potential involvement in a genetic predisposition to neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy (NESHIE). Protein products of the input set of genes are represented by blue nodes. Additional direct and secondary interactors of the input set are represented in grey.

SUPPLEMENTARY DATA A. Methods used to perform gene ontology enrichment and protein-protein interaction network analyses.

SUPPLEMENTARY DATA B. Gene Ontology enrichment results

SUPPLEMENTARY TABLE 1. Variant Details table data.

SUPPLEMENTARY TABLE 2. Ensembl Variant Effect Prediction table data.

SUPPLEMENTARY TABLE 3. Gene Details table data.

SUPPLEMENTARY TABLE 4. Gene Human Phenotype Ontology table data.

SUPPLEMENTARY TABLE 5. MutationTaster Variant Effect Prediction table data.

SUPPLEMENTARY TABLE 6. Study Details table data.

SUPPLEMENTARY TABLE 7. Study Findings table data.

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