Pipeline for identifying papers with disease or disease gene ortholog

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Aim of Project: To Use Textpresso to identify C. elegans papers that describe either orthologs of human disease genes or a model for the disease in C. elegans.

This method uses one or more categories and keywords to identify sentences in the text of the paper.

Keywords: --The keywords ‘ortholog’, ‘homolog’, ‘similar’, ‘relate’ and ‘model’ and various forms of the words as they may occur in the following example phrases:

  • is the ortholog
  • is an ortholog
  • is orthologous
  • is homologous
  • is the homolog
  • is similar to

Script looks for (an asterisk at the end denotes wild-card):

  • ortholog*
  • homolog*
  • similar
  • relate*
  • model*

The keywords ‘C. elegans’ or ‘elegans’ Example sentence: We used C. elegans as a model system for <human disease>, and other variations.


Category 1: C. elegans gene or protein

Requirement: The gene (or protein list) needs to be kept up to date with the model organism database.

Category 2: Human disease

The following sources were used to build the lexicon for the human disease category:

1. Human disease list from Neuroscience - NIFSTD owl file for class NIF-Dysfunction located at http://ontology.neuinfo.org/NIF/Dysfunction/NIF-Dysfunction.owl

2. Human disease ontology file from http://www.obofoundry.org/cgi-bin/detail.cgi?id=disease_ontology

Pick ‘term names’ and ‘synonyms’ from this ontology. The more term variations that the ‘master’ list has the better it will be for picking up terms.

3. Textpresso category file ‘disease (h. sapiens)’

4. OMIM morbid map disease terms (the first column from ftp://ftp.ncbi.nih.gov/repository/OMIM/morbidmap)

Rules for Script:

Example: The term ‘Spinal muscular Atrophy’ would have been missed because it exists in the Neuroscience list as ‘Scapuloperoneal Spinal Muscular Atrophy’ but could be found in the human disease ontology mentioned above. As of now we need the following variations for the disease terms (note the capitalization of different letters at the beginning of each word in the term):

Spinal Muscular Atrophy Spinal muscular atrophy spinal muscular atrophy (probably not used this way but safe to include)

To deal with different forms of capitalization, a case-insensitive search is done. Plurals are formed by using heuristics like myopia -> myopias atrophy -> atrophies Textpresso script cap+plural.pl handles this reasonably well.

Exclusion list for Disease Lexicon: The disease lexicon works best when screened for words that are then placed in an exclusion list. Removing these terms decreases the number of false positives for elegans literature. The exclusion list will be different for a different organism.

(variations on capitalization included): Agitated Agitation Amelia Amended Bends Confused Confusion Corn Corns Dependence Fit Hermaphroditism Hyperactivity Hypersensitivity Infection Interferon Interferons Intestinal Intestine Intestines Longevities Longevity Orf Overdose Paralysed Paralysis Prolapse Recruitment Reflux Restlessness Rupture Scar Scarring Starvation Suppression Tag Tear boil ectodermal feminization intestine leanness leannesses longevities longevity overdose recruitment rupture scar starvation temp trauma infertility infertile volvulus ganglion locally fracture disorder deformity DNA fragmentation plaque roundworm cysts anatomical abnormality unconscious tumor morphology vaccinia DNA damage convulsions seizure seizures hyperactive behavior complex I complex II acyl-CoA dehydrogenases disease

Other Exclusions: In addition to the above terms, exclude

  • any entry with string length 4 or less
  • any entry that is a C. elegans gene i.e. that matches the regex [a-z]{3}-\d+
  • generally words inside brackets will be thrown away:

(disorder) (disease) [disorder] [disease]

Sentences with these types of phrases are excluded:

  • Cancer Research Center
  • Cancer Center
  • Center for Childhood Diabetes
  • Center for Diabetes

These phrases are excluded:

  • term followed by 'cells' or 'cell line'

[eg., Similarly , ectopic expression of CED-4 in 293T human embryonic kidney cells and MCF7 breast carcinoma cells induced rapid apoptosis ( Fig . 1 ) , even though a proteolytic activity has not been ascribed to CED-4 .}

  • term followed by 'toxin' eg., diphtheria toxin
  • term followed by 'virus'

These are also excluded:

1. Articles of type: ‘meeting_abstract’ and 'Congresses'

2. Supplementary material: Doc IDs of type:WBPaper00037683.sup.1

3. ‘Materials and Methods’ section of paper

4. When matching sentences are from section ‘References’ classify paper into a separate group, so it becomes easier for curator to go through. --The script has a default mode in which it searches for relevant sentences in all fields other than references. The script has a references mode in which it runs only on sentences from references.

5. Whole genome papers Eg., Doc Id WBPaper00030997 Title: Draft genome of the filarial nematode parasite Brugia malayi. --Implemented by excluding lines that are very long. Currently, I have set this limit to 250 words i.e. If line has more than 250 words, then it is excluded.

6. Should not be picked up: relate in 'correlated' model in 'remodelling' relate in 'unrelated'

Other strategies: 1. Used the OMIM morbid map, to extract the human gene list: ftp://ftp.ncbi.nih.gov/repository/OMIM/morbidmap A preliminary run was done with the human gene list along with the disease lexicon to extract sentences that have both a human disease and a human gene. This method results in a large number of false positives. For now, this strategy will not be pursued further.


Out of 100 papers, there were 29 false positives, putting the precision at 71%.


Out of a 100 random papers that were selected from the elegans literature there were 2 papers that the script missed: (Note that these papers belong to the second class of papers of interest where one of the categories ‘elegans gene’ and the keyword ‘ortholog’, ‘homolog’, are missing).