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• Khaldi N, Wolfe KH (2008) Elusive Origins of the Extra Genes in Aspergillus oryzae. PLoS ONE 3(8): e3036. doi:10.1371/journal.pone.0003036. This was a cool but somewhat controversal finding presented at Fungal Genetics last year.
• Casselton, LA. Fungal sex genes - searching for the ancestors. doi: 10.1002/bies.20782. A review of recent findings about the Zygomycete MAT locus.
• Soanes DM, Alam I, Cornell M, Wong HM, Hedeler C, et al. (2008) Comparative Genome Analysis of Filamentous Fungi Reveals Gene Family Expansions Associated with Fungal Pathogenesis. PLoS ONE 3(6): e2300. doi:10.1371/journal.pone.0002300
• Lee DW, Freitag M, Selker EU, Aramayo R (2008) A Cytosine Methyltransferase Homologue Is Essential for Sexual Development in Aspergillus nidulans. PLoS ONE 3(6): e2531. doi:10.1371/journal.pone.0002531

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An outbreak of a fungal infection called "white-nose syndrome" is killing bats in the Northeastern US.  This New Scientist article mentions the outbreak briefly and an NPR story and recent Boston Globe story also gives it some coverage.  Sounds like we still don't know much about the causal agent or how it is killing the bats at this time, but some researchers, including Elizabeth Buckles at Cornell University, Vishnu Chaturvedi at NY State Dept of Health, and Jon Reichard at Boston University are working on it.

This is of course old news if you read what Hyphoid Logic has been saying.

That there is a previously undescribed cold loving fungus sounds very interesting, there have been some recent discoveries of psychrophilic fungi like Cryptococcus laurentii and Rhodotorula himalayensis so it would be interesting to learn more when the researchers publish some of these results.

Some more links

• Boston Globe (2008-07-28 story)
• Walking the Berkshires
• iBerkshires
• US Fish and Wildlife

Thanks Kathyrn B for reminder about this story.

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The first of several dermatophyte fungal genomes, Microsporum gypseum, has been released at the Broad's Dermatophyte site.  Two Tricophyton species and another Microsporum genome should follow soon. These dermatophyte fungi are Onygenales (Ascomycota) fungi (like Coccidioides and Histoplasma), although their placement in the phylogenies shown in the whitepaper and related review paper is a bit ambiguous. I'm sure that can be improved with a few more gene sequences gleaned from the genomes.

The 23 Mb M. gypseum genome is a bit smaller than the sizes of C. immitis (28 Mb), H. capsulatum (32 Mb), or Paracoccidioides brasiliensis (29 Mb).  While no annotation is currently available for the M. gypseum genome, this genome will help in establishing what genes were ancestral in the Onygenales and comparing patterns of gene family gains and losses in fungi that specialize on animal hosts.

Some more comparison across different kinds of dermatophyte fungi that are very distantly related like dandruff causing fungus Malasezzia globosa (Basidiomycota) will be really interesting as well.

Thanks Joe H and FGI folks for passing along announcement and to the Broad/FGI folks for the work to make this sequence available.

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Report concludes that a fungal genome database is of "the highest priority".

This is the title as listed in PubMed for this article from Future Medicine about the AAM report on charting future needs and avenues of research on the fungal kingdom.

The need for a comprehensive database for information about fungi, starting at least with systematic collections of genomic and transcript data, is highlighted as a major need.  Really and sort of new database effort should strive to be more comprehensive and include genetic and population data (alleles, strains) and information like protein-protein, protein-nucleic acid interactions (as Pedro mentioned). But on top of that it, it needs to be comparative so that information from systems that serve as great models can be transferred to other fungal systems that are being studied for their role as pathogens or interacting in the environmental.

Affordable next-gen sequencing will allow us to obtain genome and transcript sequence for basically all species or strains of interest.  Researchers with no bioinformatics support in their lab will likely be able to outsource this to a company or campus core facility.  But how can they easily map in the collective information about genes, proteins, and pathways onto this new data?  And have it be a dynamic system that can update as new information is published and curated in other systems.

I think this has to be the future beyond setting up a SGD, CGD, etc for every system.  The individual databases are useful for a large enough community where there are curators (and funding), but we will have to move to a more modular system in the future (aspects of which are in GMOD) that can have both an individual focus on a specific species/clade and a more comprehensive view of the that is comparable across the kingdom.  There are 100+ fungal genomes, but the community size for some of them are in the dozens of labs or less. How can they take advantage of the new resources without an existing infrastructure of curators?  Their systems serve an important need in a research aim, but how can discoveries there make its way back into the datastream of othe systems?

I see it as there are several ways one would interact with a system that provided single-genome tools as well as a framework for comparative information.  At a gene level, one might be looking for all information about a specific gene, based on sequence similarity searches, or starting with a cloned gene in one species. Something akin to Phylofacts or precomputed Orthogroups for defining a Gene but with more linking information about function by linking in information from all sources.  So a comparative resource, but also tapping into curated andliterature mined data.

At a genome level, one might want to do whole genome comparisons of gene content from evolutionarily defined families genes (gene family size change) or at a functional level.  To start out with, each gene/protein would already need a systematic functional mapping.  This could be as simple as running InterProScan on every protein, expanded to find Orthogroups (or OrthoMCL orthologs) and transfer function from model systems, and finally even more advanced, do further classified better with tools like SIFTER.

Interlinked with these orthologous and paralogous gene sets would be anchors for analyses of chromosomal synteny and even comparative assembly including tools like Mercator.  Certainly things like all of this exist but making it more pluggable for different sets of species would be an important additional component.

At a utility level, the gene annotation and functional mapping of all this information should be possible. I would imagine a researcher could upload the sequence assembly they received from the core facility and the system can generate multiple gene predictions, annotate the genes, and link these genes within the known orthogroups of the system (preserving their privacy for these genes if desired).  Presumably this sort of thing would be easier as a standalone in-house for the researcher, but web services could also be the place for this.

For fungal-sized genomes this amount of data is not too extereme.  Things like Genome Browser, BLAST, etc should all be rolled out of the box based on the basic builds.

On the DIY and community annotation front, there would also need to be a layer of community derived annotation that could be layered on all these systems.  I would imagine this both to be for gene structure annotation (genome annotation) and functional annotation (protein X does Y based on experiment Z, here is the journal reference).  I think aspects of this would be visible, auditable (tracked), but maybe not blessed as official until a curator could oversee these inputs. In my mind, whether or not this is in a Wiki per se or just new system that allows community input is less important to me than having it be a) structured (not a bunch of free text) b) tracked and versionable c) easy for researchers to input so that the knowledge is captured, even if it has to be reorganized later on.

Seems like a lot of work to be done, but really many of these things already exist through what  the GMOD project has built.  Many loose ends and software that doesn't fully meet up to these needs, but I think the important concept is these are all general solutions that will be of benefit to most communities, not just the fungal ones.  One lingering question I always have when approaching genomic datas

that will be dynamic, what if any of this makes its way into GenBank?  How is this sort of thing banked so that it can be captured, and does the improved functional or gene structure annotation ever make its way into the repository databases to correct and improve what has already been submitted there?

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The Cornell Mushroom Blog has an excellent video of Coprinopsis growing and some discussion about these mushrooms.

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Mike Challen has summarized discussion at two recent conferences regarding a Basidiomycete Research Network at his blog in a post on BRN - Summary of Discussions, 14/07/08.

In particular it is important to establish a community network that will help basidiomycete labs. There is also a strong need for shared approaches for effective use the genomic data from the more than a dozen basidiomycete genomes currently being sequenced.

Mike's blog is open for discussion on the topic and I hope you'll weigh in on suggestions for how the community can better communicate and share ideas.

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The American Academy of Microbiology has released a report (PDF) on the Fungal Kingdom outlining importance of research in the kingdom and recommending several areas of priority for future areas of research.

One recommendation that makes the top of the list is an integrated database for fungal genomes, something we're keenly interested in seeing happen.  This sort of centralized repository of functional annotation, literature links, and genome sequences and annotation is critical given the 150+ genomes that are available or on their way.  Systematic re-annotation with consistent tools, comparative analyses and gene predictions, and linking gene sequences by homology and ortholog predictions are a critical component to fully utilizing the genomic data that has been produced for the fungi and other organisms.

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This is a research blog so I though I'd post some quick numbers we are seeing for de novo assembly of the Neurospora crassa genome using Velvet. The genome of N.crassa is about 40Mb and sequencing of several flow cells using Solexa/Illumina technology to see what kind of de novo reconstruction we'd get. I knew that this is probably insufficient for a very good assembly given what has been reported in the literature, but sometimes it is helpful to give it a try on local data.  Mostly this is a project about SNP discovery from the outset. I used a hash size of 21 in velvet with an early (2FC) and later (4FC) dataset. Velvet was run with a hashsize of 21 for these data based on some calculations and running it with different hash sizes to see the optimal N50.  Summary contig size numbers come from the commands using cndtools from Colin Dewey.

  faLen < contigs.fa | stats

2 flowcells (~10M reads @36bp/read or about 10X coverage of 40Mb genome)

            N = 199562
          SUM = 25463251
          MIN = 49
 1ST-QUARTILE = 87
       MEDIAN = 107.0
 3RD-QUARTILE = 146
          MAX = 5371
         MEAN = 127.59568956
          N50 = 130

            N = 102437
          SUM = 38352075
          MIN = 41
 1ST-QUARTILE = 77.0
       MEDIAN = 153
 3RD-QUARTILE = 467
          MAX = 7189
         MEAN = 374.396702363
          N50 = 837

So that's N50 of 837bp - for those used to seeing N50 on the order or 1.5Mb this is not great.  But from4 FC worth of sequencing which was pretty cheap.  This is a reasonably repeat-limited genome so we should get pretty good recovery if the seq coverage is high enough. Using Maq we can both scaffold the reads and recover a sufficient number of high quality SNPs for the mapping part of the project.

To get a better assembly one would need much deeper coverage as Daniel and Ewan explain in their Velvet paper and shown in Figure 4 (sorry, not open-access for 6 mo). Full credit: This sequence was from unpaired sequence reads from Illumina/Solexa Genomic sequencing done at UCB/QB3 facility on libraries prepared by Charles Hall in the Glass lab.

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NPR had a story this weekend on Cocoa plantation collapse and the ecological aftermath of the changes the witches' broom fungus Moniliophthora perniciosa has wreaked. The genome sequence project for this Homobasidiomycete fungus (also known as Crinipellis perniciosa, phylogenetic relationships discussed by Aime and Philips-Mora 2005) is underway at the Laboratory Genomica e Expressao at UNICAMP, Brazil.  The witches's broom (not this witches' broom) is named because of the bristly form it induces in the cacao plants.

The genome project will hopefully improve the diagnosis and treatment work that is needed.  Beyond the insatiable need for chocolate, the NPR story does talk about the impact on farmers, the economy, and the environment with the loss of these cacao plantations.

• A Not-So-Sweet Lesson from Brazil's Cocoa Farms
• Witches' Broom and Frosty Pod waft deadly through the jungle night
• Link from Ohio State University Cacao disease research
• STATUS OF CACAO WITCHES' BROOM: Biology, Epidemiology, and Management, Annual Review of Phytopathology

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Lam’s research indicates that adding pedobacter to the skin of mountain yellow-legged frogs would lessen the effects of Batrachochytrium dendrobatidis (Bd), a lethal skin pathogen that is threatening remaining populations of the frogs in their native Sierra Nevada habitats. Lam first conducted petri dish experiments that clearly showed the skin bacteria repelling the deadly fungus. She then tested pedobacter on live infected frogs, bathing some of them in a pedobacter solution. The frogs bathed in pedobacter solution lost less weight than those in a control group of infected frogs that were not inoculated. In addition to the lab experiments, the JMU and SFSU researchers have studied the yellow-legged frogs in their natural habitats and discovered that some populations with the lethal skin disease survive while others go extinct. The populations that survived had significantly higher proportions of individuals with anti-Bd bacteria. The results strongly suggest that a threshold frequency of individuals need to have anti-Bd bacteria to allow a population to persist with Bd. (from Eureka alert)

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We're excited that a Penicillium marneffei grant to Mat Fisher and collaborators has been funded by the Welcome Trust. It includes a collaboration with University College London, our lab, JCVI, and Univ of Melbourne. This project will explore functional and comparative genomics approaches to studying the fungus which primarily infects immune compromised individuals in south-east asia where it is found associated with bamboo rats. 

Scientists at Imperial College London have received almost £350 000 from the Wellcome Trust, the UK's largest medical research charity, to study Penicillium marneffei, the only Penicillium fungus to cause serious disease in humans. The researchers aim to find out what makes this particular fungus pathogenic.

Read the rest of the release.

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Just finished attending Genetics and Cell Biology of Basidiomycetes in Cape Girardeau, MO which was an intimate gathering of basidiomycetaphiles.  I learned about systems that are used for studying fruiting body development, genetic mapping, pheromone and mating genes, kinesin dynamics, meoitic gene regulation, and a host of topics.  I'm happy I got a chance to meet more folks in the community and learned about where informatics and computational approaches are really needed to push along some of the interpretation of the more than a dozen basidiomycete genomes.  In particular it sounds like the Pleurotus, Schizophyllum, Agaricus bisporus, and Serpula genomes are all marching along to completion with some already in 4X assembly or further.  

So we'll further have more samples from of key model and some less-model species to assist researchers working on many different mushroom-forming fungi that range from brown and white-rotting saprophyte fungi to mycorrhizal fungi that associate with plants.    I'm excited about the work to make transformation and knockouts more readily in these systems too to push the genetics and cellular biology of these systems even further.  The genome sequences will be another tool in these endeavors.

The last day ended with a discussion about genome annotation and future support for curating gene models.  Basically everyone is unhappy with computational predictions and want to be able to go in and fix things. (I think people remember the ones that are gotten wrong more readily than the ones that were right, but computational prediction definitely performs poorly in some situations).   In this Web 2.0-land we live in, this is still not something easily done with any of the freely available genome browsing tools. The JGI's browser was lauded for its ability to handle these kinds of requests, but how do we proceed when genomes are not sequenced by that center or when (not too distant future) communities are able to sequence a genome themselves using 454/Illumina-Solexa/Helicos/Pacific Biosystems approaches in their own lab?  There is still a huge lag in what kinds of tools researchers can use to annotate genomes to fix gene models and add functions.  Hopefully projects like GMOD will continue to develop useful tools for solving these needs, but there is certainly a need for better support of distributed community annotation of genomes where this little direct money for supporting curators from a single place.

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The fuel is recovered by distillation, but there are about six gallons of leftovers for every gallon of fuel that's produced. Those leftovers, known as stillage, contain solids and other organic material. Most of the solids are removed by centrifugation and dried into distillers dried grains that are sold as livestock feed, primarily for cattle. The remaining liquid, known as thin stillage, still contains some solids, a variety of organic compounds from corn and fermentation as well as enzymes. Because the compounds and solids can interfere with ethanol production, only about 50 percent of thin stillage can be recycled back into ethanol production. The rest is evaporated and blended with distillers dried grains to produce distillers dried grains with solubles. The researchers added a fungus, Rhizopus microsporus, to the thin stillage and found it would feed and grow. The fungus removes about 80 percent of the organic material and all of the solids in the thin stillage, allowing the water and enzymes in the thin stillage to be recycled back into production. The fungus can also be harvested. It's a food-grade organism that's rich in protein, certain essential amino acids and other nutrients. It can be dried and sold as a livestock feed supplement. Or it can be blended with distillers dried grains to boost its value as a livestock feed and make it more suitable for feeding hogs and chickens.

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This month's Genetics has a series of articles exploring the genome (published last year & freely available at Science) of the green algae Chlamydomonas reinhardtii. These manuscripts are primarily genome analyses making for a very bioinformatics focused issue of Genetics. Some of the highlights include:

• Exploration of snoRNAs finding that a large fraction are clustered in the genome and located in introns.
• Description of transcription factors and their evolutionary conservation and potential link to multicellularity.
• Duplication and diversification of the RNA processing machinery for small RNA mediated silencing.
• Gleaning additional information from Chlamy ESTs that have been over-trimmed.
• Integrating metabolomics and proteomics into better genome annotation.
• Evolution of signaling proteins found in multicellular animals and now Chlamydomonas.

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