MalaCards: an amalgamated human disease compendium with diverse clinical and genetic annotation and structured search

Abstract

The MalaCards human disease database (http://www.malacards.org/) is an integrated compendium of annotated diseases mined from 68 data sources. MalaCards has a web card for each of ∼20 000 disease entries, in six global categories. It portrays a broad array of annotation topics in 15 sections, including Summaries, Symptoms, Anatomical Context, Drugs, Genetic Tests, Variations and Publications. The Aliases and Classifications section reflects an algorithm for disease name integration across often-conflicting sources, providing effective annotation consolidation. A central feature is a balanced Genes section, with scores reflecting the strength of disease-gene associations. This is accompanied by other gene-related disease information such as pathways, mouse phenotypes and GO-terms, stemming from MalaCards' affiliation with the GeneCards Suite of databases. MalaCards' capacity to inter-link information from complementary sources, along with its elaborate search function, relational database infrastructure and convenient data dumps, allows it to tackle its rich disease annotation landscape, and facilitates systems analyses and genome sequence interpretation. MalaCards adopts a 'flat' disease-card approach, but each card is mapped to popular hierarchical ontologies (e.g. International Classification of Diseases, Human Phenotype Ontology and Unified Medical Language System) and also contains information about multi-level relations among diseases, thereby providing an optimal tool for disease representation and scrutiny.

Figure 1.

Overlaps among disease sources. (A) Venn diagram for the four major MalaCards name sources, according to MalaCards mapping. (B) A symmetric matrix showing the number of overlapping diseases between all pairs of primary name sources according to MalaCards mapping. Shading (as per color bar) and numerals represent degree of overlap in disease counts. Source abbreviations: DO– Disease Ontology, GR- Gene Reviews, NIH RD– NIH Rare Diseases, GT- GeneTests, GHR- Genetic Home Reference, NINDS– National Institute of Neurological Disorders and Stroke.

Figure 2.

Distributions for disease-gene relations. Solid black – diseases per gene, dashed black – genes per disease, solid grey – diseases per elite gene, dashed grey – elite genes per disease.

Figure 3.

Distribution of MalaCards Information Score (MIFTS). Grey – status in version 1.03 (2013), black – the current version 1.11. MIFTS values have almost doubled, from an average of 12.2 ± 10.3 to 22.5 ± 16, reflecting the progress made over three years in the knowledge recorded in MalaCards.

Figure 4.

The average number of gene-disease associations across all compared sources for the set of 37 compared diseases.

Figure 5.

Inter-source gene set comparison. (A) Left, black: Correlation between MalaCards gene rank vector and the consensus rank; Right, grey: Standard deviation of the difference between the MalaCards gene rank and the consensus rank. (B) Left, black: The number of MalaCards gene disease association in the top 20 consensus rank; Right, grey: The maximal consensus gene rank for a MalaCards gene. Raw data values for each disease are given in Supplementary Table S3.