Specialty Genes Overview
Specialty Genes refers to the special classes of genes that are of particular interest to infectious disease researchers, such as antibiotic resistance genes, virulence factors, drug targets, and human homologs.
For each specialty genes class, PATRIC:
- Collects reference gene sets from popular and community recognized external databases, many of which are manually curated based on literature.
- Creates our own database of manually curated reference gene sets based on literature, as needed, to provide more accurate and comprehensive information for NIAID select pathogens.
- As part of genome annotation, maps reference genes to their homologs based on high sequence similarity using BLASTP, and thus, providing consistent annotation of specialty genes across all bacterial genomes.
- Makes specialty genes accessible and usable by providing specialized analysis and search tools to allow researchers to quickly select potential targets for the development of drugs, vaccines, and therapeutics.
Classes and Data Sources of Specialty Genes in PATRIC
- Antibiotic Resistance Genes: Antibiotic Resistance refers to the ability of bacteria to develop resistance to antibiotics through gene mutation or acquisition of antibiotic resistance genes. We have integrated and mapped known antibiotic resistance genes from the following sources:
- Drug Targets: Drug Targets are proteins being targeted by known, approved, or experimental small molecule drugs. We have integrated and mapped such drug targets from the following sources:
- Human Homologs: Human Homologs are the bacterial proteins that share high sequence similarity with human proteins. We have integrated and mapped proteins from the Reference Human Genome available at NCBI RefSeq .
- Virulence Factors: Virulence Factors are the gene products that enable bacteria to establish itself on or within a host organism and enhance its potential to cause disease. We have integrated and mapped virulence factor genes from the following sources:
*Note: PATRIC_VF is a manually curated virulence factor database, which contains the genes identified as playing a role in virulence in certain organisms. Each PATRIC_VF gene is linked to one or more journal articles that establish its virulence based on experimental evidence. For more details, see PATRIC_VF FAQs.
Mapping Specialty Genes to PATRIC Proteins
For each class of specialty genes, we gather reference gene sets from the data sources described above. We create specialized BLAST databases using protein sequences for each reference gene set, which are then used as part of the genome annotation pipeline. For each genome in PATRIC, we take all predicted protein sequences and search them against each of the specialized BLAST databases using BLASTP.
The top BLAST hits are parsed and filtered based on sequence identity and sequence coverage using the following criteria:
(%Query coverage >=80 OR %Subject coverage >=80) AND %Identity >=80
For identifying Human Homologs, we use:
(%Query coverage >=50 OR %Subject Coverage >=50) AND %Identity >=50
All the BLAST hits that pass the above-mentioned similarity criteria are further classified as follows using field “Evidence”.
- Literature: For any BLAST hit, if the query and the subject genes are the same, i.e. the same genes in the same genome based on locus tag or some other identifier match, we designate the Evidence as “Literature”. This means that there is direct literature evidence describing the gene in question, which probably characterizes the gene based on experimental evidence.
- *Note: even when a hit is classified as “Literature”, sequence coverage and/or percent identity for the sequence similarity could still be below 100%, because of the differences in the start site of the same gene as predicted by different annotation systems.
- BLASTP: For all BLAST hits that are not classified as “Literature”, we designate the Evidence as “BLASTP”. This means that the gene in question is highly similar to a specialty gene described in one of the source databases. However, the reference gene may or may not be exactly the same gene and/or in the same genome.
Accessing Specialty Genes on the PATRIC Website
At PATRIC, you can access specialty genes and related information in the following ways:
- Using the Specialty Genes Data Summary available under the “Data” Tab in the main navigation along the top of the PATRIC site. Here you can view summaries of selected genomes, related tools and tutorials, and diagrams of how we curate, map, and integrate Specialty Genes.
- Via the “Specialty Genes” Tab on any taxon or genome “Overview” page. Here you’ll find a pre-scoped Specialty Genes List. See next question for more details on what you can do from this list.
- As a tabular summary entitled Specialty Gene Summary at the bottom of any taxon or genome “Overview” page. See example.
- As a tabular summary entitled Special Properties at the bottom of a gene “Overview” page. See example.
- Using the Specialty Genes Search, which allows researchers to find specialty genes in their organisms/genomes of interest based on taxonomy, special property, and keyword.
- *Note: Search results are displayed in a Specialty Genes List, described below.
Specialty Gene List and Related Filters
The Specialty Gene List provides the following information:
- Information about PATRIC genes, such as Genome Name, PATRIC and RefSeq Locus Tags, Gene Names, and Products.
- Information about the matching specialty gene in the reference database, such as Property, Source Database Name, Source ID, Classification, and PubMed references. Source IDs are linked to the corresponding pages on the Source Database websites where you can access more information. PubMed links take you to the corresponding references lists at PubMed.
- Summaries of sequence similarity from BLASTP hit, such as Percent Query Coverage, Percent Subject Coverage, and Percent Identity.
The Specialty Gene List can be filtered using the progressive filters available in the left-hand panel as follows:
- Filter by Keyword: Search using any keywords related to the Organism Name, Gene Name, Locus Tag, or Gene Product and find matching specialty genes.
- Filter by Property: Select one or more classes of specialty genes, such as Antibiotic Resistance Genes, or Virulence Factors.
- Filter by Source: Select one or more source databases to see genes similar to the reference genes from those databases.
- Filter by Evidence: Hits designated as “Literature” imply that the query and the subject genes are the same, i.e. the same genes in the same genome based on locus tag or some other identifier match, however, there may be some differences in the start site. It means that there is direct literature evidence describing the gene in question, which probably characterizes the gene based on experimental evidence. All other hits designated as “BLASTP” imply that the gene in question is highly similar to a reference gene described in one of the source databases. However, the reference gene may or may not be exactly the same gene and/or in the same genome.
- Filter BLAST Hits by Source Organism: This allows researchers to find BLAST hits where the query organism is the same as the source organism. The filter can be used to find hits from the same genome, same species, or the same genus thus removing any hits based on other organisms.
- Filter BLAST Hits by Sequence Similarity: This allows researchers to filter hits by applying different cut-offs for percent query coverage, percent subject coverage, and/or percent identity.