Disease and Drugs

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C. elegans as a model system to study disease and disease genes

Major areas for which worm models of human disease exist

Instead of a paper-by-paper approach for disease curation, a big picture/disease topic approach may be more practical, to begin with we can make sure these major disease classes, also represented by the most number of elegans papers, are in WB.

1. Neuromuscular diseases:

Amyotrophic Lateral Sclerosis, Duchenne Muscular Dystrophy, Friedreich’s Ataxia, Inclusion Body Myositis, Spinal Muscular Atrophy

  • Human genes: SOD1, TDP43, DMD, FXN, APP, SMN
  • elegans counterparts: sod-1, tdp-1, dys-1, frh-1, apl-1, smn-1)

2. Complex neurological diseases:

  • Parkinson’s disease: modeling via transgenic expression of human genes alpha-synuclein (PARK1); *Genes involved: leucine-rich repeat kinase 2 (LRRK2, also known as PARK8); ubiquitin E3 ligase (PARK2); kinase PINK1 (PARK6); oncogene DJ-1 (PARK7); Elegans model also used to study neurotoxic and neuroprotective compounds.
  • Alzheimer’s disease and Tauopathies:
  • Human genes APP, PSEN1, PSEN2 and MAPT gene encoding tau
  • elegans apl-1, elegans presenilins-sel-12, hop-1, spe-4 ; elegans effectors of transgenic expression of tau: sut-1, sut-2.
  • Autism spectrum disorders: Human Shank family proteins, neuroligins, neurexins;

Elegans: shn-1, nlg-1, nrx-1.

3. Ciliary diseases:

Cystic kidney dieases: Polycystic kidney disease (PKD)

  • Human genes PKD1, PKD2.

Elegans: lov-1, pkd-2

Autosomal recessive polycystic kidney disease

  • Human Genes Tg737orpk, hetrotrimeric kinesin-II, KIF3A, KIF17
  • Elegans: osm-5, klp-11, klp-20, kap-1, osm-3;

Bardet-Biedl syndrome

  • human genes-BBS genes
  • Elegans: bbs genes


  • human genes-NPHP1, NPHP2, NPHP3, NPHP4
  • elegans genes: M28.7, T28D6.4, klc-1, klc-2, R13H4.1.

4. Laminopathic diseases:

Mutations in lamin (LMNA) cause: Emery-Dreifuss muscular dystrophy (EDMD)

  • human gene: Emerin
  • elegans: emr-1

LMNA-related congenital muscular dystrophy (L-CMD)

Limb-girdle muscular dystrophy and dilated cardiomyopathy

Neuropathic Charcot-Marie-Tooth disorder

Lipodystrophies: Mandicyloacral dysplasia, Dunnigan-type familial partial lipodystrophy

Systemic premature aging syndromes: Hutchison-Gilford progeria, Werner syndrome

5. Intestinal inflammatory diseases:

Ulcerative colitis

Crohn’s disease

Necrotizing enterocolitis (NEC)

Human gene: Toll-like Receptor 4 (TLR4)

6. Obesity

7. Prion diseases

Human disease relevance descriptions (moved from concise descriptions page)

C. elegans has been established as the simplest animal model available for human disease. We have made orthologs of human disease genes, a priority list for curation. In the past, information about the relevance to human disease was to a large extent based on sequence comparison of the related human gene and it's elegans ortholog. This resulted in a scripted description for the elegans gene, that mentioned the human ortholog, the disease caused when the human gene is mutated, and the related OMIM identifiers. We have now begun a more detailed updating of these descriptions, and the writing of new ones, based on the published literature, where elegans is used to model the biology of a disease and/or the orthologous elegans gene function is studied in detail. We have developed a method to identify and flag these papers using a Textpresso (www.textpresso.org) keyword and category based search.

A new database tag 'Human disease gene relevance' was introduced so that we can highlight and make this data available for use by both the elegans as well as the non-elegans biomedical researcher.

This tag will be used to:

--hold OMIM data that is currently in concise descriptions

--highlight how studies in elegans has contributed to understanding of human disease

Database mappings between OMIM accession numbers and OMIM web pages already exist in WormBase. Otherwise for every accession we would have to include the URL_constructor? So for this accession number it would be "http://omim.org/entry/605248"

Paul Davis: Yes you are right the OMIM database object is populated in the build....not very well(contains the old ncbi data), but we can address this issue. As far as the postgress to .ace dump, what you have in the example is fine, you don't need anything else. The url constructor is contained in the ?Database object so we don't need any additional .ace from your end. The only real question we have to resolve is that omim.org use a ID system where they have #*^. characters prefixing their very unique string IDs. The special characters aren't any good for us and their web team don't even use them for their website for this exact reason.

As the Accession/ID is just a numerical string this causes us a problem as there are other databases out there who also adopt this nomenclature and so you get collision between the data sets (in acedb). We would like to propose adding OMIM: to the ID/accession but this messes with the url constructor.

Todd, could you handle this at the website end to convert OMIM:605248 -> http://omim.org/entry/605248 (need to confirm this around the time data is uploaded).

Human disease relevance descriptions

Human disease relevance descriptions were introduced in late 2011, on the WormBase gene page, to serve both the worm researcher and the biomedical researcher from outside the worm community. This description alerts researchers to the fact that the worm is either an effective model system or is being developed as a model system to study the disease/gene. For under-studyed genes in elegans for which there are only sequence names, human ortholog and disease information provide clues to the function of the gene.

Human disease relevance descriptions are written in most cases, to include:

  • Orthology to the human disease gene or family of genes, may include domain information.
  • The different types of human diseases known to have mutations in the human gene ortholog. OMIM accession numbers are provided below the description which are links into the OMIM resource.
  • Functional similarities or differences between the human/vertebrate and worm gene.
  • Data from worm studies that add new knowledge, or validate existing knowledge from studies in other species or experimental systems (eg., cell culture, etc.).
  • For understudyed genes in elegans for which there are only sequence names, human ortholog and disease information provide insights into elegans gene function
  • Also serves the purpose of making automated descriptions more information-rich and useful to users:

Examples of automated descriptions based on OMIM orthology that existed in WormBase prior to 2012:

1. T27A3.6 is orthologous to the human gene MOLYBDENUM COFACTOR BIOSYSTHESIS PROTEIN E (MOCS2; OMIM:603708), which when mutated leads to disease.

2. Y24D9A.8 is orthologous to the human gene TRANSALDOLASE 1 (TALDO1; OMIM:602063), which when mutated leads to disease.

3. Y110A7A.9 is orthologous to the human gene KIAA1351 PROTEIN (WDR11; OMIM:606417), which when mutated leads to disease.

For WormBase Progress Report (written May/June 2012)

In recent years, C. elegans has been widely used as a system to study human disease gene orthologs and to model human disease and drug-disease interactions. In early 2012, we began writing ‘Human Disease Relevance’ descriptions, as an addition to the gene pages, keeping in mind the non-worm biomedical community. These descriptions combine information obtained from automated ortholog identification methods which are mostly based on sequence, with curated information about disease modeling, from the published worm literature. These descriptions include the following information: (1) Orthology to the human disease gene or family of genes and domain information (2) Diseases associated with mutations in the human gene, with OMIM accessions which are links into the OMIM resource (Online Mendelian Inheritance in Man; http://www.ncbi.nlm.nih.gov/omim) (3) New information or validations that studies in C. elegans have yielded to the study of disease gene/disease. Currently, we have 80 of these descriptions in the database. --End report--

C. elegans as a model to study infectious agents

Bacteria and Biofilms
Parasitic nematodes
Fungal pathogens
  • human fungal pathogen Cryptococcus neoformans

Textpresso keyword search 'Cryptococcus neoformans' returns 117 documents

C. elegans as a model to study metal toxicity and detoxification

Using C. elegans to study the effects of space flight

WormBase contributions to the Disease Ontology

Disease Ontology contributions and related issues

Acedb model changes for human disease data in WB

Model changes to capture and consolidate human disease data

OA for gene-disease information

Specifications for the OA for WBGene-disease

Textpresso-based systems to flag papers

Pipeline for identifying papers with disease or disease gene ortholog

Pipeline for identifying papers with drugs

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