The following questions focus on concerns specific to GO annotation of plant associated microbes and the use of GO to capture the Pto DC3000 - Plant Interaction. A list of questions relevant to the generic implementation of GO can be found on the GO FAQ page of the Gene Ontology website.
1. Interpreting and using annotations in the Pto-Plant Interaction Model
Why do GO terms use the word "symbiont" instead of "pathogen"?
Pathogenesis often includes the proliferation or reproduction of a microbe in a plant or animal host. The extent to which such proliferation and accompanying microbial processes are detrimental (and thus pathogenic) to the host depends on many factors, including the biotic or abiotic environment and the physiology of the host, especially the strength of the defense response. The identical microbe or host process can be beneficial or detrimental depending on the context. For example, necrotrophy associated with the plant hypersensitive response to biotrophic and hemibiotrophic pathogens, while involving some host cell death, can be considered beneficial to the host. The pathogen is curtailed at the point of infection and denied access to any living tissue at the necrotic front. On the other hand, for necrotrophs that live on exudates from dead tissues, the identical type of cell killing is beneficial to the pathogen. These examples illustrate the difficulties confronted by PAMGO and the GO Consortium when considering whether newly developed GO terms that describe processes involved in pathogen-host interactions (e.g. GO:0044406, “adhesion to host”) should be made “child” terms (i.e. subterms) of the existing GO term “pathogenesis” (GO:0009405). Because such processes, even in the same microbe, might be part of initiating either a pathogenic or a more neutral interaction depending on the specific circumstances, we decided against such placement in the GO. Instead, we adopted “symbiosis” as a general term with its proper broad definition encompassing the whole spectrum of intimate relationships (see GO:0044403). The GO definition of this term notes that “mutualism, parasitism, and commensalism are often not discrete categories of interactions and should rather be perceived as a continuum of interaction ranging from parasitism to mutualism.” This definition also specifies that the word “host” refers to “the larger (macro) of the two members of a symbiosis,” and that the word “symbiont” is used for “the smaller (micro) member.” Accordingly, we adopted the word “symbiont” to designate the microbe in those GO terms that relate to microbe-host interactions. [adapted from Torto-Alalibo et al, manuscript in preparation for BMC Microbiology]
Why can't I find a term for induction of the hypersensitive response?
The underlying philosophy of GO requires that GO terms be defined using language that is meaningful across many pathosystems. The phrase “hypersensitive response” serves as a useful example. While this term is commonly used among plant pathologists to refer to rapid defense-associated plant cell death at the site of infection, to researchers in animal systems it can have very different allergy-related or behavioral connotations. Therefore, newly developed PAMGO terms avoid using “hypersensitive response” in the term name and instead use term names such as “modulation by symbiont of host defense-related programmed cell death” (GO:0034053) to annotate such bacterial effector activity. At the same time, the previously existing GO term “hypersensitive response” (GO:0009626) was modified at the request of PAMGO collaborators to “plant-type hypersensitive response,” thus clearly matching the new term name with the existing GO definition, which specified plant cells. It is important to note that an investigator searching GO terms for “hypersensitive response” would be pointed to both terms named above by means of the synonym field attached to each GO term. Finally, these two terms illustrate the difference between terms appropriate for annotating genes in the microbe, or symbiont (GO:0034053) versus those in the plant (GO:0009626) that are involved in the process described. In cases where the symbiont gene product induces a hypersensitive reponse, the gene product has been annotated to the term:
GO:0034055: positive regulation by symbiont of host defense-related programmed cell death
In cases where the symbiont gene product induces a hypersensitive response via interaction with an identified resistance gene, the following annotation can be additionally used:
GO:0052527: positive regulation by symbiont of host resistance gene-rdependent defense response
Why can't I find a term for induction of necrosis?
The underlying philosophy of GO requires that GO terms be defined using language that is meaningful across many pathosystems. As for the phrase “hypersensitive response”, "necrosis" serves as a useful example. Among plant pathologists, "necrosis" is typically used to refer to localized death of cells or tissues. In contrast, researchers in animal systems use necrosis to refer to cell death secondary to traumatic injury and closely linked to the inflammatory response. Modulation of lesion formation is captured in the Pto DC3000 - Plant Interaction Model with the term:
What terms are used to distinguish the role of effectors in PAMP-triggered immunity and effector-triggered immunity?
Terms relating to induction and suppression of PAMP triggered immunity (PTI) are captured by the terms:
GO:0052033: pathogen-associated molecular pattern dependent induction by symbiont of host innate immunity GO:0052034: negative regulation by symbiont of pathogen-associated molecular pattern-induced host innate immunity
In contrast, there are no terms that include the specific phrase "effector-triggered immunity". Rather, the existing terms are designed to capture modulation of host defense-related programmed cell death (i.e. the hypersensitive response) or host resistance gene-dependent defense response (used when the response results from interaction with an identified resistance gene). Relevant terms include:
GO:0034055: positive regulation by symbiont of host defense-relatedprogrammed cell death (used when a symbiont gene product induces a hypersensitive response in the host) GO:0034054: negative regulation by symbiont of host defense-relatedprogrammed cell death (used when a symbiont gene product suppresses a hypersensitive response induced by a second gene product)
GO:0052527: positive regulation by symbiont of host resistancegene-dependent defense response (used when a used when a symbiont gene product induces a hypersensitive response in the host via interaction with an identified host resistance gene) GO:0033660: negative regulation by symbiont of host resistancegene-dependent defense response (used when a used when a symbiont gene product supresses a hypersensitive response in the host resulting from interaction of a second gene product with an identified host resistance gene)
Why can't I find terms that specify activation, induction, or suppression?
In some cases, users may look for but not find the terms activation, induction, or suppression used in conjunction with a biological process of interest. During the process of term development, members of the PAMGO Consortium decided that in general it was simplest to use the term "positive regulation" to encompass "activation, "induction" and "up-regulation" and the term "negative regulation to encompass "suppression" and "down-regulation". Doing so not only streamlines the range of terms, but also enables annotation to proceed in cases where the starting state is unknown. That is, "activation" implies that the process in question was not occuring prior to its initiation by the gene product being annotated while "up-regulation" implies that the gene product being annotated merely increased the level of a pre-existing process. "Positive regulation" encompasses either possibility. It should be noted that activation, induction, and suppression have been incorporated into the GO database as synonyms such that a search employing those terms will point users to the appropriate alternate term.
How can I indicate that a particular gene product is secreted or translocated by a given secretion pathway?
According to current GO conventions, the biological process terms "Protein secretion by the type XXX secretion system" and cellular complex terms "Type XXX protein secretion system complex" are reserved for components of the secretion pathway and are NOT to be used to annotate the secreted/translocated proteins themselves. Because of the desire among PAMGO members to capture the mechanism of translocation, particularly for the Type III effectors, biological process terms with the following wording were created "Interaction with host via protein secreted by the type XXX secretion system". For the Type III effectors, the following term is used:
GO:0052049: interaction with host via protein secreted by type III secretion system
How can defense-related programmed cell death be distinguished from other types of cell death?
Distinguishing the specific process leading to visually-scored cell death can be difficult, particularly when deciding whether to annotate to GO:0034055: positive regulation by symbiont of host defense-related programmed cell death or its more general parent term, GO:0001907 : killing by symbiont of host cells. Data considered while making this distinction include the presence of resistance genes in the host known to recognize the effector in question, impact of the effector on symbiont growth, and additional genetic factors present in the symbiont. Levels of effector in the host are also considered, given that overexpression may lead to non-specific cell death. Consequently, effector and helper genes have been annotated to the term GO:0034055: positive regulation by symbiont of host defense-related programmed cell death when host cell death is observed upon delivery of the effector or helper by the Type III secretion system. Cell death resulting from transient expression in the host, in the absence of other evidence, has been described with the less specific term, GO:0001907 : killing by symbiont of host cells
Can biological process annotations describing the interaction between organisms be made using data acquired by transgenic expression of symbiont gene products in the host?
Data from transgenic expression of symbiont genes in the host is being used to determine cellular locations and molecular functions of the symbiont gene products. However, it has been decided that biological process annotations will only be made when the gene product is delivered to the host by the symbiont. In the case of Type III effectors this implies delivery by the T3SS.
How can I contribute annotations for plant genes involved in the interaction between organisms?
The primary focus of PAMGO has been the creation of terms for annotating gene products in plant-associated microbes and the use of these terms for annotating specific gene products in the target set of organisms. GO annotations for over 1200 Arabidopsis gene products can be found at the GO database, and suggestions for new annotations made through the TAIR Gene Ontology Resources. Gene Ontology terms for rice (Oryza sativa) are also supported by the GO Database and can be browsed at the Gramene Ontologies Database.
I can't find the exact term I need in the
Pto-Plant Interaction Model or GO database. Should I just use the term that seems closest to what I'm looking for?
Creation of GO terms is a work in process and that the biological process, molecular function, or cellular component to which you wish to annotate may not yet exist. Please contact the PPI site administrator to request a particular term. Do not, however, annotate to a term that seems "good enough" but not quite right. This approach has led to mistaken annotation of host gene products to terms designed for symbiont gene products, among other errors.
Are the effector annotations in the Pto-Plant Interaction Model present in the GO database?
Effector annotations for Pto DC3000 are present in the GO database, though since any changes occur first to the Pto-Plant Interaction Model, there may be a short lag between their appearance in the model and in GO. For the sake of completeness, annotations for effectors present in P. syringae strains other than Pto DC3000 are being included in the Pto-Plant Interaction Model. These will not, however, be forwarded to GO.
How does the information shown here differ from that in the Gene Ontology database?
While Gene Ontology annotation has been used as the guide for capturing information on various P. syringae virulence factors, formatting has been adapted and the "host interactor" field added to better meet the specific needs of the P. syringae research community. Among the differences in formatting are the addition of a "reference" field showing the first author and publication date of the relevant publication, and the addition of gene /protein names to the "with" field. The "host interaction" field has been added for the purpose of capturing the broader impact on host response (beyond merely the binding of specific host proteins)
Where can I find annotations for plant genes involved in the interaction between organisms?
The primary focus of PAMGO has been the creation of terms for annotating gene products in plant-associated microbes and the use of these terms for annotating specific gene products in the target set of organisms. GO annotations for over 1200 Arabidopsis gene products can be found at the GO database, and suggestions for new annotations made through the TAIR Gene Ontology Resources. Gene Ontology terms for rice (Oryza sativa) are also supported by the GO Database and can be browsed at the Gramene Ontologies Database.
Magdalen Lindeberg
PPI Project Coordinator
Dept Plant Pathology
Cornell University contact
