Exome sequencing and the management of neurometabolic disorders” , download article here

The metabolic evaluation of the child with an intellectual developmental disorder: Diagnostic algorithm for identification of treatable causes and new digital resource, download article here.


Compared to the human reference genome, a single exome can reveal over 120,000 variations. In order to facilitate the discovery of causal variations, filters such as frequency, mutation type, and mode of genetic inheritance are often employed. However, even after filtering for rare non-synonymous mutations, over 50 candidate genes may remain. Manually going over the literature for each gene and matching to the clinical phenotype is time consuming and inefficient.
To speed up the process of literature review, Warren Cheung from the Wasserman lab has designed a tool called MeSHOP.

The tool is useful when the researcher has a clinical phenotype in mind and wishes to know what genes are associated with that term. Simply supplied with a MeSH (Medical subject heading) reflecting the clinical phenotype, the program looks at the PubMed articles for each gene and extracts a list of over-represented MeSH terms. It then builds an internal “dictionary” based on that list and evaluates the strength of association between a gene and the input query. For output, the program summarizes a list of ranked genes predicted to be associated to the MeSH input above a chosen statistical threshold.

As proof of concept, in one TIDEX family, the proband displays symptoms of biotin abnormality. We used “biotin” as the query to MeSHOP, and overlapped the output genes against our variations. Among the 70+ candidate genes, only ACACB is shown to have relevance to biotin, and clinical follow-ups are in progress. MeSHOP is a novel way of prioritizing genes using pre-existing literature in a speedy and automated manner.