Fungal growth and knockout phenotype resources

SCOPING BIOLOGY_DOMAIN

Species: SCHPO, yeast

Fungal growth and knockout phenotype resources

Bottom line: we surveyed fungal datasets that record how strains or
mutants grow on defined carbon and nitrogen sources, to see whether they can
serve as evidence in gene reviews. Two kinds exist. Species-level growth
profiles, such as FUNG-GROWTH, say what a fungus can eat but not which gene
does the work. Mutant phenotype data does name genes. For our two largest
fungal gene sets it is already curated and downloadable: 147 of 149 reviewed
S. pombe genes and 222 of 224 reviewed S. cerevisiae genes have curated
mutant phenotypes, and 64 and 61 of them respectively have a carbon- or
nitrogen-source growth phenotype other than ordinary growth on glucose. Almost
all of those come from two high-throughput screens that GO curators have not
turned into annotations, and most hits are indirect (spindle checkpoint and
respiratory-assembly mutants failing on alternative carbon sources). They are
evidence of necessity, not participation, so they can support or question an
annotation but should not create one. Beyond the two model yeasts, the only
fungal genome-wide fitness data across many carbon sources is RB-TDNAseq in
the basidiomycete yeast Rhodotorula toruloides (downloadable; 6,409 genes with
data); our analysis of it is in FUNGAL_PHENOTYPES/RHOTO.md.
No filamentous-fungus knockout collection has been screened across carbon or
plant-biomass sources; there, carbon phenotypes survive only as hit lists and
figures in individual papers.

Species-level growth: FUNG-GROWTH

FUNG-GROWTH (de Vries et al. 2025,
Microbiol Resour Announc, doi:10.1128/mra.00378-25) holds growth profiles
for 398 fungi across the kingdom, most with a public genome, on about 36
substrates: 10 monosaccharides, 5 oligosaccharides, 11 polysaccharides, 7
crude plant biomasses and controls. Growth is scored against glucose and
no-carbon plates. It is meant to sit beside JGI MycoCosm CAZyme annotations.

Mutant phenotypes for reviewed yeast genes

scripts/phenotype_overlap.py (in the FUNGAL_PHENOTYPES/ folder)
joins every genes/SCHPO and genes/yeast review, by the PomBase or SGD
cross-reference in its UniProt record, to the PomBase single-locus haploid
phenotype file (FYPO terms) and SGD's phenotype_data.tab (APO terms). Output:
FUNGAL_PHENOTYPES/data/reviewed_gene_phenotypes.tsv, one row per reviewed
gene with its phenotype counts, its nutrient phenotypes and their references,
and the review actions on its IMP rows.

S. pombe (PomBase) S. cerevisiae (SGD)
Reviews with a database cross-reference 149 224
...with any curated mutant phenotype 147 222
...with a non-glucose carbon/nitrogen-source phenotype 64 61

A phenotype counts as nutrient utilisation when its label names a carbon or
nitrogen source. Rows about glucose (the standard medium, so a general growth
defect) and "normal growth" rows are excluded.

Where the nutrient phenotypes come from

Screen Organism Reviewed genes with a hit Cited in our GOA files
Rodríguez-López et al. 2023, PMID:37787768, deletion library across many conditions S. pombe 61 0
VanderSluis et al. 2014, PMID:24721214, prototrophic deletion collection on 4 carbon × 7 nitrogen sources S. cerevisiae 50 0
Dudley et al. 2005, PMID:16729036, 4,710 mutants under 21 conditions S. cerevisiae 17 0
Malecki et al. 2016, PMID:27887640, and Malecki & Bähler 2016, PMID:27918601, respiratory growth screens S. pombe 6 and 5 0

Across PomBase as a whole, Rodríguez-López 2023 supplies 11,403 of these
non-glucose nutrient rows, covering 2,610 genes; in SGD, VanderSluis 2014
supplies 2,553 rows over 1,417 genes.

What the hits look like

Most are indirect. Spindle checkpoint genes (bub1, mad3) and autophagy
genes (atg2, atg5) show altered growth on galactose or on lysine and
proline nitrogen sources; mitochondrial assembly factors (ATP10, ATP11,
COX20, COX23) fail on glycerol and lactate because they are needed for
respiration, not because they act on those carbon sources. Under the
participation rule in CLAUDE.md, a knockout growth defect shows that a gene
is necessary, and necessity is not evidence of taking part in the process.
This is the likely reason curators have left the screens out of GO.

Suggested use in reviews:
- Corroborate an existing pathway annotation when the mutant fails on the
pathway's own substrate.
- Flag a pathway annotation for a second look when the mutant grows normally
on that substrate.
- Do not propose NEW process terms from these phenotypes alone.

Other fungal knockout and fitness datasets

We checked whether each dataset's phenotype table can actually be
downloaded. PMIDs were verified in PubMed. "Yes" means a test download
succeeded and the file opened. Conditions are summarised with carbon and
nitrogen sources flagged.

Genome-wide fitness with many carbon sources

Dataset Organism Mutants × conditions Carbon / nitrogen sources Download
Kim et al. 2021, PMID:33585414 (RB-TDNAseq; includes Coradetti 2018 data) Rhodotorula toruloides 6,409 genes with data × 27 conditions Glucose, cellobiose, xylose, arabinose, galactose, mannose, acetate, lactate, oleic acid, p-coumarate, ferulate, benzoate, sugar alcohols, pentuloses; valine, leucine and phenylalanine as carbon sources Yes. Frontiers supplement Table_2.XLSX, sheet "RB-TDNA Seq" (ids RTO4_<n>), CC BY
Coradetti et al. 2018, PMID:29521624 R. toruloides 6,558 genes Glucose, oleic and ricinoleic acid; auxotrophy media Yes. eLife supp2 xlsx, CC BY
Rodríguez-López et al. 2023, PMID:37787768 S. pombe 3,509 deletions × 131 conditions (450,844 rows, with p-values) Glycerol, galactose, fructose, maltose, sucrose, mannitol, xylose, ethanol; glutamate, proline, lysine, serine Yes. eLife supp1 xlsx (39 MB), CC BY. The curated subset is already in PomBase (above)
Yeast Phenome, Turco et al. 2023, PMID:37235661 S. cerevisiae 4,554 genes × 14,484 harmonised screens (includes Hillenmeyer 2008, Dudley 2005, Qian 2012) YPG, YPL, YPE, galactose, raffinose, maltose and others Yes. yp_haphom_20221025.tar.gz (637 MB) from the project's Google Cloud bucket; licence not stated

The bacterial Fitness Browser (Price et al. 2018, PMID:29769716) is the model
for this kind of data, but its 2026 figshare archive lists only bacteria and
archaea; there is no fungal organism in it. Its site sits behind a Cloudflare
challenge and could not be fetched from our environment.

Pathogenic yeasts

Dataset Organism Scope Download
Homann et al. 2009, PMID:20041210 Candida albicans ~160 TF knockouts × ~107 conditions, incl. no carbon source, galactose, glycerol, GABA/proline nitrogen Yes. PLoS supplement s007.xls, CC BY
CGD phenotype file C. albicans and other Candida 27,890 curated rows, incl. Homann, Noble 2010 (PMID:20543849) and Segal 2018 transposon essentiality (PMID:30377286); ~200 carbon-source rows Yes. candidagenome.org/download/phenotype/, updated weekly
Jung 2015 (PMID:25849373), Lee 2016 (PMID:27677328), Jin 2020 (PMID:32839469) Cryptococcus neoformans TF, kinase and phosphatase knockout phenomes, about 30 conditions each; mostly stress, drug and virulence; galactose only Yes. Nature Communications supplements, CC BY
Billmyre et al. 2025, PMID:40402997 C. neoformans Transposon essentiality and fluconazole fitness for 6,975 genes; no carbon conditions Yes. PLoS Biol supplement

Other transposon sets (Grech 2019 S. pombe Hermes, PMID:31077324; SATAY,
PMID:28481201) cover essentiality and drugs, not nutrients.

Filamentous fungi

No filamentous-fungus knockout collection has been screened across a panel of
carbon or plant-biomass sources. Carbon phenotypes exist only as short hit
lists or figures.

Dataset Organism Scope Download
Carrillo et al. 2020, PMID:33138786 Neurospora crassa 1,168 knockouts × 10 growth and development traits; no carbon sources Yes. BMC supplement xlsx (NCU ids), CC BY
Son et al. 2011, PMID:22028654 Fusarium graminearum 657 TF knockouts × 17 traits, incl. minimal versus rich medium; CMC conidiation in a separate table Yes. PLoS supplement, ordinal scores, CC BY
PHI-base (v4 CSV, PHI-base 5 export, GAF) Pathogens, incl. F. graminearum, M. oryzae, A. fumigatus 24,123 interaction rows; virulence plus an in vitro growth field; PHI-base 5 uses PHIPO, which has carbon-source terms Yes. GitHub PHI-base/data. Licence statements conflict (CC BY vs CC BY-ND)
Coradetti et al. 2012, PMID:22532664 N. crassa TF knockout screen on Avicel, xylan, sucrose Hits in text; no per-strain table found
Brown et al. 2013, PMID:23800192 Aspergillus nidulans Non-essential kinases and phosphatases screened for cellulase production Results in figures only
Wu et al. 2020, PMID:32111691 N. crassa RNA-seq on 40 carbon sources; growth for ~8 TF mutants Supplement xlsx not opened
Lu et al. 2014, PMID:25299517 Magnaporthe oryzae 104 Zn2Cys6 TF knockouts; olive oil as carbon source Phenotypes in PDF only
Kun et al. 2021, PMID:34114741, and other de Vries lab papers Aspergillus niger Regulator knockouts (XlnR, AraR, ClrA/B, AmyR) on wheat bran and polysaccharides Per-paper figures; no consolidated table
Furukawa et al. 2020, PMID:31969561 Aspergillus fumigatus COFUN library, 484 TF knockouts; antifungal screens, no carbon sources Supplement not retrieved

FungiDB's search service now needs a registered API key, so its phenotype
tracks could not be pulled. Only 1 of our 73 filamentous-fungus and Candida
reviews (EMENI brlA) appears in PHI-base, as expected for a pathogen database.

Suggested next steps

  1. R. toruloides is the best fungal test bed: genome-wide fitness on 20
    carbon sources, the same kind of data as the bacterial Fitness Browser,
    and the closest match to FUNG-GROWTH's substrate panel. The analysis in
    FUNGAL_PHENOTYPES/RHOTO.md maps it to UniProt,
    finds 137 genes with strong carbon-source-specific defects and lists
    candidates for the first R. toruloides gene reviews.
  2. Extend phenotype_overlap.py to Candida (CGD file) and to the
    Rodríguez-López quantitative table, so reviews can quote fitness values,
    not just curated labels.
  3. For A. niger and T. reesei CAZyme reviews, pair FUNG-GROWTH species
    profiles with the de Vries lab regulator knockouts, curated by hand.

Reproducing

uv run python projects/FUNGAL_PHENOTYPES/scripts/phenotype_overlap.py

The R. toruloides scripts and their order are listed on
FUNGAL_PHENOTYPES/RHOTO.md.

Downloads are cached in tmp/fungal_phenotypes/ (gitignored).