Data Sources

Detailed statistics about Neurocarta data can be found here:

Additional resources have been investigated and discarded for various reasons. More information can be found here.

Data extraction from external sources

We have defined stringent criteria for automatic inclusion of data from external sources, with the goal of limiting the inclusion of unreliable data or information that we deem of limited utility to our target audience. In this section we provide details of procedures for each resource.

OMIM [1]: The OMIM data files (morbidmap.txt and mim2gene.txt) are downloaded from the OMIM FTP site. We extract unique mappings between Phenotype MIM numbers and Gene MIM numbers from morbidmap.txt and map the genes to their NCBI identifiers in mim2gene.txt.

RGD [2]: The RGD Gene-Disease association files (homo_genes_rdo, mus_genes_rdo, rattus_genes_rdo) are downloaded from the RGD FTP site. Annotations with the following evidence codes are ignored: ISS (redundant across species), NAS (non-traceable author’s statements are debatable), IEA (electronic annotations come from other sources (e.g. GAD) and we prefer to get these annotations directly from the source). Annotations without a PubMed reference are ignored as well.

CTD [3]: The CTD Gene-Disease association file (CTD_genes_diseases.tsv) is downloaded from the CTD website. We only consider curated annotations with Direct Evidence set to “marker/mechanism” or “therapeutic”, and at least one PubMed reference.

NIH GWAS Catalog [16]: The GWAS catalog is downloaded from NHGRI website ( We only consider variants that fall within a single and non-ambiguous gene.

Disease-specific databases: The SFARI [4] annotation files (autism-gene-dataset.csv, gene-score.csv) are downloaded form the SFARI Gene website. Each PubMed reference is imported as separate literature evidence in Neurocarta, with the option of it being defined as “negative” whenever specified in the annotation file. The PDGene [5], AlzGene [6], and MSGene [7] “Top Results” are extracted from their respective websites. All three databases assess their results for their epidemiological credibility using two methods: (1) The HuGENet interim criteria for the cumulative assessment of genetic associations [12, 13], and (2) Bayesian analyses [14, 15]. Only meta-analysis results with P-values <0.00001 are considered.The “Hot gene list” from ADHDgene [8] is extracted from their website. This list includes all genes that have been identified in at least five independent studies. The ALSoD [9] top 20 genes are identified through the credibility score analysis provided on their website. The genes are ranked by number of affected patients and by number of mutations per gene, and the ranks are summed to determine the final rank for each gene. For the IDGene [10] and EpiGAD [11] databases, we wanted to extract more information than what was readily accessible through the websites. We manually reviewed the genes listed in each database and used that information as a seed for targeted PubMed searches and manual curation of relevant publications.

Disease mapping from external sources to Disease Ontology (DO) terminology

For the disorder-specific databases we use the corresponding appropriate terms in DO (e.g. “autism spectrum disorder” for SFARI and “amyotrophic lateral sclerosis” for ALSoD). As described next, for other databases we used a combination of automatic and semi-automatic methods for mapping.

OMIM, RGD, and CTD: These three resources provide OMIM or MeSH terms that we mapped to DO terms as follows. First, we use the Xref mappings provided in the Human_DO.obo ontology file, which covers about 50% of the phenotype-gene mappings in these resources. For the remaining that use terms lacking a DO Xref, we use the NCBO Annotator Web service [5] followed by manual quality control to resolve partial matches, increasing coverage substantially. In total about 2/3 of the phenotype-gene associations present in OMIM, RGD, or CTD could be mapped to a DO term. This is due to non-disease terms that are listed in OMIM but not in DO (e.g. “Blood type”, “Ig levels”), and some disease terms missing from DO (mostly syndromic, e.g. TARP syndrome, Jawad syndrome), or missed mappings. We have notified the DO maintainers of these gaps and expect to eventually be able to import a greater fraction of these annotations into Neurocarta.

GWAS Catalog: This resource doesn’t use a controlled vocabulary for their disease/trait terminology. We rely entirely on the NCBO Annotator Web service [5] followed by manual quality control for the mappings to the Disease or Phenotype Ontologies.

Manual curation of the literature

While the Neurocarta framework is generic, our curation team is focusing on annotations relevant to our primary research interest, neurodevelopmental disorders. In-depth annotations have been produced on the following Disease Ontology terms (including respective children terms): (i) “Autism Spectrum Disorder” (ASD; DOID_0060041); (ii) “Cerebral Palsy” (CP; DOID_1969); (iii) “Fetal Alcohol Spectrum Disorder” (FASD; DOID_0050696); (iv) “Epilepsy” (DOID_1826); and (v) and “Intellectual disability” (DOID_1059). When necessary, phenotype descriptions were complemented with more descriptive Human or Mammalian Phenotype Ontology terms such as “Memory impairment” (HP_0002354), “EEG abnormality” (HP_0002353), or “decreased brain size” (MP_0000774). Curators review the literature using PubMed searches across all fields (that is, the default PubMed setting) using queries such as “epilepsy” AND “genetics”. We avoid making searches that are gene-centric, except as a secondary mechanism to find additional citations on a gene-phenotype relationship identified through initial screening. When possible, review papers are used to identify primary research papers, which are then curated as “Experimental Type Evidence”. The curators record details about the experiment using controlled vocabularies, categorized as (for example) “Bio Source”, “Experiment Design”, or “Developmental Stage”. The criterion for inclusion is an experimentally-supported statement linking the gene to the phenotype. The exception is genome-wide studies where the results were not yet confirmed by follow-up experiments. The curated papers involve a wide variety of experiments including both animal models and human studies. For the former, if the authors describe the animal model as a specific model for the disorder of interest, the curators associate the gene studied in the paper directly to the human disease. If the authors describe an endophenotype that is related to the disease, the gene is associated to the endophenotype only. In some cases, review papers are used as the source of the annotations instead of drilling down to the original research papers. In that case, it is curated as “Literature Type Evidence” with no details about the experiments. To help users navigate through the evidence, we are, when possible, associating phenotypes to genes in a species-specific way. So, for instance, if the evidence comes from an experiment done in rats, it will be linked in Neurocarta to the rat gene.



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OMIM = Online Mendelian Inheritance in Man
RGD = Rat Genome Database
CTD = Comparative Toxicogenomics Database
SFARI Gene = Simons Foundation Autism Research Initiative Gene Database
PDGene = Parkinson’s Disease Gene Database
AlzGene = Alzheimer’s Disease Gene Database
MSGene = Multiple Sclerosis Gene Database
ADHDgene = Attention Deficit Hyperactivity Disorder Gene Database
ISS = Inferred from Sequence or Structural Similarity
NAS = Non-traceable Author Statement
IEA = Inferred from Electronic Annotation
PMID = PubMed ID
ID = Intellectual Disability
epiGAD = Epilepsy Genetic Association Database
ALSoD: Amyotrophic Lateral Sclerosis Online Genetics Database