matchbox: An open-source tool for patient matching via the Matchmaker Exchange

Abstract

Rare disease investigators constantly face challenges in identifying additional cases to build evidence for gene-disease causality. The Matchmaker Exchange (MME) addresses this limitation by providing a mechanism for matching patients across genomic centers via a federated network. The MME has revolutionized searching for additional cases by making it possible to query across institutional boundaries, so that what was once a laborious and manual process of contacting researchers is now automated and computable. However, while the MME network is beginning to scale, the growth of additional nodes is limited by the lack of easy-to-use solutions that can be implemented by any rare disease database owner, even one without significant software engineering resources. Here we describe matchbox, which is an open-source, platform-independent, portable bridge between any given rare disease genomic center and the MME network, which has already led to novel gene discoveries. We also describe how matchbox greatly reduces the barrier to participation by overcoming challenges for new databases to join the MME.

Deleterious de novo variants of X‐linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita

“…For family 22, trio WGS was performed on saliva DNA at Baylor Genome Center as part of the NIH Gabriella Miller Kids First Research Program. For this family, the GeneMatcher and matchbox nodes of the Matchmaker exchange database were used to obtain collaborations using the search term ZC4H2 (Arachchi et al, ; Philippakis et al, ; Sobreira et al, ). For family 24 trio WES was performed at Fulgent Genetics, US.…”

MAGEL2‐related disorders: A study and case series

“…The GeneMatcher (http://genematcher.org) and matchbox nodes of the Matchmaker exchange database were used to obtain collaborations and additional patient profiles, using the search term MAGEL2 …”

“…The GeneMatcher (genematcher.org) and matchbox nodes of the Matchmaker exchange database were used to obtain collaborations and additional patient profiles, using the search term MAGEL2. [10][11][12] ExPASy database was used to predict the protein translation from the mRNA sequences of MAGEL2, and the protein translations were subjected to basic local alignment search tool searches. 13,23 The R statistical environment was used for all mutational analysis computing.…”

“…The gene MAGEL2 , which resides in the PWS locus, is a single‐exon gene encoding the melanoma‐antigen‐subfamily‐like‐2 protein and is part of a large ubiquitination complex that regulates endocytosis, receptor recycling and cell‐surface localization. In mouse models, Magel2 regulates the cell cycle, neuronal signal transduction, neurite growth, and muscle function . Because the maternal genetic region is silenced through methylation, all classes of mutations in the maternal MAGEL2 allele are clinically insignificant .…”

“…In mouse models, Magel2 regulates the cell cycle, neuronal signal transduction, neurite growth, and muscle function. [7][8][9][10][11][12][13] Because the maternal genetic region is silenced through methylation, all classes of mutations in the maternal MAGEL2 allele are clinically insignificant. 4 However, pathogenic mutations on the paternal allele, which is expressed, are detrimental to neural and muscular development and are responsible for a number of human syndromes.…”