 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Oct 23, 2023 |
| Title |
Unbiased discovery of natural sequence variants that influence fungal virulence |
| Organism |
Cryptococcus neoformans |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Isolates of Cryptococcus neoformans, a fungal pathogen that kills almost 200,000 people worldwide each year, differ at a few thousand up to almost a million DNA sequence positions compared to a 19-megabase reference genome. We used bulked segregant analysis and association analysis, genetic methods that require no prior knowledge of sequence function, to address the key question of which naturally occurring variants influence fungal virulence. We identified a region containing such variants, prioritized them, and engineered strains to test our findings in a mouse model of infection. At one locus we identified a 4-nt variant in the PDE2 gene, which severely truncates its phosphodiesterase product and significantly alters virulence. Our studies demonstrate a powerful and unbiased strategy for identifying key genomic regions in the absence of prior information, suggest revisions to our assumptions about cAMP levels and about common laboratory strains, and provide significant sequence and strain resources to the community.
|
| |
|
| Overall design |
Comparative expression between KN99a and C8 strains of Cryptococcus neoformans before and after culture ifor 24 hours in RPMI + 10% mouse serum (37°C, 5% CO2).
|
| |
|
| Contributor(s) |
Agustinho DP, Brown HL, Chen G, Brent MR, Doering TL |
| Citation(s) |
37898126 |
| BioProject |
PRJNA967729 |
| Submission date |
May 12, 2023 |
| Last update date |
Jan 22, 2024 |
| Contact name |
Michael Brent |
| E-mail(s) |
brent@wustl.edu
|
| Phone |
314-660-2205
|
| Organization name |
Washington University
|
| Street address |
4515 McKinley Ave
|
| City |
St Louis |
| State/province |
Missouri |
| ZIP/Postal code |
63110 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL27451 |
Illumina NextSeq 500 (Cryptococcus neoformans) |
|
| Samples (16)
|
|
| Supplementary file |
Size |
Download |
File type/resource |
| GSE232437_PRJNA967729_geo_processed.csv.gz |
115.9 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...