Modeling data for Infectious agents

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C. elegans serves as an infection model for various bacteria, fungi and nematodes, in order to study:

  • host genes involved in infection and resistance
  • bacterial virulence factors
  • to identify effective drugs
  • drug screening for infectious diseases

Model Proposal for ?Infection_assay

?Infection_assay  Public_name ?Text
		  Summary Text  //This describes how the experiment was done and what is the result 
	          Interacting_strain   Host_strain ?Strain //for worm strains
                                       Pathogen_strain ?Strain //for bacteria, fungi and viral strains
		  Effect_on_nematode   Phenotype_observed	?Phenotype
				       Phenotype_not_observed	?Phenotype
                  Resistance	Resistance_host_gene ?Gene  //host gene required for infection
                                Resistance_molecule ?Molecule //molecules required for infection to happen
                                Resistance_treatment Text //certain treatments required for infection to happen
                  Hypersensitive	Hyper_sensitive_gene ?Gene ?Text //gene whose activity confers resistance or sensitivity to infection
                             		Hypersensitive_allele ?Variation ?Text //allele whose activity confers resistance or sensitivity to infection
                             		Hypersensitive_drug ?Molecule ?Text //molecules whose activity confers resistance or sensitivity to infection
                             		Hypersensitive_treatment ?Text ?Text //treatment whose activity confers resistance or sensitivity to infection, second text is the effect of the treatment
		  Regulates_expression  Expression_cluster  ?Expression_cluster XREF Infection_assay
					Up_regulates_gene   ?Gene #Evidence //gene whose expression is increased in response to infection
					Down_regulates_gene ?Gene #Evidence //gene whose expression is decreased in response to infection
                  Remark Text   
		  Reference  ?Paper



  • It seems by 'Requires_treatment Text //certain molecules required for infection to happen' you might mean 'Requires_treatment Text //treatment required for infection to happen'--kjy (talk) 23:39, 10 March 2014 (UTC)
  • The Modifying_influence tags should be characterized as things that alter infection susceptibility - they can either cause hypersusceptibility or resistance to the infection. --kjy (talk) 23:39, 10 March 2014 (UTC)
  • Can we call 'Reagent' 'Interacting_organisms'?--kjy (talk) 01:59, 14 February 2014 (UTC)
  • Should add 'Fungal_strain'--kjy (talk) 01:59, 14 February 2014 (UTC)
    • 'Viral_strain' as well? -XW
    • (Mary Ann) - You should be able to extract whether the Reagent is a fungal/viral/whatever strain by following through from the Strain object to the Species. So, simply adding the Strain name here should be sufficient for the website to display the taxonomic info. Maybe this is preferable to adding lots of new tags?
  • I would change 'symptom' to 'Effect_on_nematode', to capture 'lethal', 'slowed_growth' etc. phenotypes. --kjy (talk) 01:59, 14 February 2014 (UTC)
  • Although we put Resistant to and susceptibility to pathogen terms in the phenotype ontology, perhaps we should consider moving them out to be organism interaction tags, along with other organism relationship terms such as symbiotic, mutualistic, etc., afterall, shouldn't we have a way to represent Heterorhabditis bacteriophora and its enteric bacterium, Photorhabdus luminescens. I know this is an infection model, but if we go this way, perhaps we should consider opening it up a bit broader to reflect all organism-organism relationships (I guess that also suggests we should change the title of the model to 'Strain_exposure_assay?) --kjy (talk) 01:59, 14 February 2014 (UTC)
  • Dependency can go both ways - the gene, molecule, treatment can be required for either susceptibility or resistance. --kjy (talk) 01:59, 14 February 2014 (UTC)
  • The Resistance supertag is not quite right. An allele can also confer susceptibility. So perhaps it should be called 'Modifying_influence'; that is, these objects do not define the outcome of the exposure to the possible pathogen, but alter the normal outcome --kjy (talk) 01:59, 14 February 2014 (UTC)
  • Some grammar points: 'Regulate_expression' -> 'Regulates_expression', 'Up_regulate_gene' -> 'Up_regulates_gene', 'Down_regulate_gene' -> 'Down_regulates_gene'--kjy (talk) 01:59, 14 February 2014 (UTC)
  • Chris' comments March 11, 2014:

1.) So I/we are all clear, a new ?Infection_assay object will be created for every Strain-Strain (Host-Pathogen) interaction per paper that the interaction appears in, correct?

2.) For the line:

Infection_model_description Text // proposed by Ranjana

Can we provide a better comment of what this is supposed to be in the description (other than "proposed by Ranjana")?

3.) For the line:

Interacting_organism  ?Strain //include worm, bacteria, fungi and virus strains

Maybe "Interacting_organism" should be "Interacting_strain" as it is more clear for curators and those reading the model. Also, maybe to clear things up we could have sub-tags inside of "Interacting_organism/strain" tag that are "Host_strain" and "Pathogen_strain" like this:

Interacting_strain  Host_strain  ?Strain  // nematode host strain of infection
                    Pathogen_strain  ?Strain  // pathogenic strain (bacteria, fungi, virus, etc.) causing the infection

4.) For the line:

Infection_dependency Requires_gene ?Gene  //genes that make infection happen

Can we change "Requires_gene" to "Requires_host_gene" and change "genes that make infection happen" to "host gene required for infection"

5.) For the "Modifying_influence" tag, can we add a '//' comment to the Gene line that says 'gene whose activity confers resistance or sensitivity to infection" and likewise for the allele, molecule, and treatment comments change them to "allele/molecule/treatment that confers resistance or sensitivity to infection"?

6.) For the line:

Treatment Text Text//treatment that resist infection, first text describe the treatment, second text is the effect of the treatment

I'm not sure what advantage we gain by splitting up the treatment and effect descriptions into two "Text" entries. If you really want to distinct descriptions, why not give them separate tag names?

7.) And, just for clarity in the model, can we add a '//' comment to the "Up_regulates_gene" and "Down_regulates_gene" tag lines that says "gene whose expression is increased(decreased) in response to infection"?

Model Proposal for ?Gene

The Experimental_model tag refers to ?DO_term (disease), in cases of study of infectious agents using Elegans, it is not so much a 'disease model' as an infection model. It's a bit silly to talk about elegans as a model for dysentery, as compared to saying it is an infection model for the bacteria, Shigella flexneri, which is the pathogen in dysentery.

We will attach this information to Gene, analogous to disease information (similar to the Experimental_model and Potential model tags for Gene). Initially I thought of tagging Genes just as 'Infection_model' but I think it's worthwhile to actually delineate this a bit further and tag genes as either needed for pathogen infection or resistance to it, thus the 'Required_for_infection' and 'Resistance_to_infection' tags.

Proposal 1

 Current Gene model:
 Disease_info 	Experimental_model  ?DO_term  XREF  Gene_by_biology        ?Species    #Evidence	            
              	Potential_model	    ?DO_term  XREF  Gene_by_orthology      ?Species    #Evidence
              	Disease_relevance   ?Text                                  ?Species    #Evidence 
 Add under ?Gene:

 Infection_model     Required_for_infection       ?Strain   XREF  Host_gene_required_for_infection    ?Species    #Evidence  
                     Resistance_to_infection      ?Strain   XREF  Host_gene_required_for_resistance   ?Species    #Evidence
                     Infection_model_description  ?Text                                               ?Species    #Evidence


Curating information about the infectious agent-Proposal for ?Strain:

As was suggested for capturing information about the bacterial strain/species for GO data, we will use the ?Strain model:

Add to Strain model:

 Infection_model_info             Host_gene_required_for_infection    ?Gene  XREF  Required_for_infection
                                  Host_gene_required_for_resistance   ?Gene  XREF  Resistance_to_infection
                                  Infection_model_description       ?Text  ?Species  #Evidence

Example for Proposal 1

  • WBPaper00027729: The Caenorhabditis elegans ABL-1 Tyrosine Kinase Is Required for Shigella flexneri Pathogenesis

 In this example the data points are:
 Gene Required_for_infection = abl-1 (WBGene00000018)
 The bacterial strain = Shigella flexneri strain 2457T     
 Infection_model_description, is basically a concise description that will describe the model, similar to the 'Disease_relevance' description 
 under Disease_info in ?Gene.
 Infection_model     Required_for_infection       ?Strain   XREF  Host_gene_required_for_infection    ?Species    #Evidence  
                     Resistance_to_infection      ?Strain   XREF  Host_gene_required_for_resistance   ?Species    #Evidence
                     Infection_model_description  ?Text                                               ?Species    #Evidence

 I'd also like to be explicit about the species, as it might be easier for web scripts to pull information if it's right there.  But Kevin's point  
 taken that it is a redundant since ?Strain has ?Species information. 

 Modeled in .ace file as:
 Gene : "WBGene00000018"
 Required_for_infection       "2457T"    "Shigella flexneri"    Paper_evidence  "WBPaper00027729" 
 Required_for_infection       "2457T"    "Shigella flexneri"    Curator_confirmed "WBPerson324"                      
 Required_for_infection       "2457T"    "Shigella flexneri"    Date_last_updated "2014-02-12"
 Infection_model_description  "The gram-negative bacterium Shigella flexneri is the causative agent of Shigellosis, a diarrheal disease that affects
 millions of people every year; the study of Shigellosis in vivo has been hampered by the lack of a suitable model system; studies in the 
 whole-animal model system C. elegans, have shown that S. flexneri kills worms by an infection-like process that requires live bacteria, 
 correlates  with the bacterial accumulation in the intestine, and requires the S. flexneri virulence plasmid which is crucial for pathogenesis in  
 mammalian systems; in addition, the elegans Src homology, non-receptor tyrosine kinase ABL-1, is required for S. flexneri-induced killing, as loss of  
 ABL-1 through mutation, RNA interference(RNAi), or pharmacological inhibition via the inhibitor STI571, results in extension of nematode life span on  
 S. flexneri."      "Shigella flexneri"   Paper_evidence  "WBPaper00027729"

Different scenarios with Strain information:

  • authors may not always mention the strain for the pathogen
  • may reference an older paper and things could get messy from there, if I have to identify which exact strain they used based on the older paper.

In these cases, I'd like to use ?Species (when strain information is hard to find). Not sure it is absolutely important to curate to the level of strain! However when strain information is present, the following model lets me curate to that level of granularity:

Proposal 2

                     Required_for_infection_by_strain     ?Strain    XREF   Host_gene_required_for_infection    #Evidence 
                     Resistance_to_infection_by_strain    ?Strain    XREF   Host_gene_required_for_resistance   #Evidence
                     Required_for_infection_by_species    ?Species   XREF   Host_gene_required_for_infection    #Evidence
                     Resistance_to_infection_by_species   ?Species   XREF   Host_gene_required_for_resistance   #Evidence    
                     Infection_model_description          ?Text      ?Species                                   #Evidence


 Infection_model_info             Host_gene_required_for_infection      ?Gene  XREF  Required_for_infection_by_strain
                                  Host_gene_required_for_resistance     ?Gene  XREF  Resistance_to_infection_by_strain
                                  Infection_model_description           ?Text    #Evidence   

 Infection_model_info             Host_gene_required_for_infection      ?Gene  XREF  Required_for_infection_by_species
                                  Host_gene_required_for_resistance     ?Gene  XREF  Resistance_to_infection_by_species
                                  Infection_model_description           ?Text    #Evidence

Proposal 3

After discussions with the Caltech group, here is a more simplified model that takes into account that the same gene might be an infection_model for more than one type of pathogenic strain:


 Infection_model  Required_for_infection        ?Text  UNIQUE  ?Strain  XREF   Host_gene_required_for_infection    #Evidence
                  Required_for_resistance       ?Text  UNIQUE  ?Strain  XREF   Host_gene_required_for_resistance   #Evidence

 Infection_model_info  Host_gene_required_for_infection    ?Gene  XREF   Required_for_infection    #Evidence
                       Host_gene_required_for_resistance   ?Gene  XREF   Required_for_resistance   #Evidence  

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