Large-scale genomic analyses with machine learning uncover predictive patterns associated with fungal phytopathogenic lifestyles and traits.

Invasive plant pathogenic fungi have a global impact, with devastating economic and environmental effects on crops and forests. Biosurveillance, a critical component of threat mitigation, requires risk prediction based on fungal lifestyles and traits. Recent studies have revealed distinct genomic patterns associated with specific groups of plant pathogenic fungi. We sought to establish whether these phytopathogenic genomic patterns hold across diverse taxonomic and ecological groups from the Ascomycota and Basidiomycota, and furthermore, if those patterns can be used in a predictive capacity for biosurveillance. Using a supervised machine learning approach that integrates phylogenetic and genomic data, we analyzed 387 fungal genomes to test a proof-of-concept for the use of genomic signatures in predicting fungal phytopathogenic lifestyles and traits during biosurveillance activities. Our machine learning feature sets were derived from genome annotation data of carbohydrate-active enzymes (CAZymes), peptidases, secondary metabolite clusters (SMCs), transporters, and transcription factors. We found that machine learning could successfully predict fungal lifestyles and traits across taxonomic groups, with the best predictive performance coming from feature sets comprising CAZyme, peptidase, and SMC data. While phylogeny was an important component in most predictions, the inclusion of genomic data improved prediction performance for every lifestyle and trait tested. Plant pathogenicity was one of the best-predicted traits, showing the promise of predictive genomics for biosurveillance applications. Furthermore, our machine learning approach revealed expansions in the number of genes from specific CAZyme and peptidase families in the genomes of plant pathogens compared to non-phytopathogenic genomes (saprotrophs, endo- and ectomycorrhizal fungi). Such genomic feature profiles give insight into the evolution of fungal phytopathogenicity and could be useful to predict the risks of unknown fungi in future biosurveillance activities.

Survey of Early-Diverging Lineages of Fungi Reveals Abundant and Diverse Mycoviruses.

Mycoviruses are widespread and purportedly common throughout the fungal kingdom, although most are known from hosts in the two most recently diverged phyla, Ascomycota and Basidiomycota, together called Dikarya. To augment our knowledge of mycovirus prevalence and diversity in underexplored fungi, we conducted a large-scale survey of fungi in the earlier-diverging lineages, using both culture-based and transcriptome-mining approaches to search for RNA viruses. In total, 21.6% of 333 isolates were positive for RNA mycoviruses. This is a greater proportion than expected based on previous taxonomically broad mycovirus surveys and is suggestive of a strong phylogenetic component to mycoviral infection. Our newly found viral sequences are diverse, composed of double-stranded RNA, positive-sense single-stranded RNA (ssRNA), and negative-sense ssRNA genomes and include novel lineages lacking representation in the public databases. These identified viruses could be classified into 2 orders, 5 families, and 5 genera; however, half of the viruses remain taxonomically unassigned. Further, we identified a lineage of virus-like sequences in the genomes of members of Phycomycetaceae and Mortierellales that appear to be novel genes derived from integration of a viral RNA-dependent RNA polymerase gene. The two screening methods largely agreed in their detection of viruses; thus, we suggest that the culture-based assay is a cost-effective means to quickly assess whether a laboratory culture is virally infected. This study used culture collections and publicly available transcriptomes to demonstrate that mycoviruses are abundant in laboratory cultures of early-diverging fungal lineages. The function and diversity of mycoviruses found here will help guide future studies into mycovirus origins and ecological functions.IMPORTANCE Viruses are key drivers of evolution and ecosystem function and are increasingly recognized as symbionts of fungi. Fungi in early-diverging lineages are widespread, ecologically important, and comprise the majority of the phylogenetic diversity of the kingdom. Viruses infecting early-diverging lineages of fungi have been almost entirely unstudied. In this study, we screened fungi for viruses by two alternative approaches: a classic culture-based method and by transcriptome-mining. The results of our large-scale survey demonstrate that early-diverging lineages have higher infection rates than have been previously reported in other fungal taxa and that laboratory strains worldwide are host to infections, the implications of which are unknown. The function and diversity of mycoviruses found in these basal fungal lineages will help guide future studies into mycovirus origins and their evolutionary ramifications and ecological impacts.

[Resection of a giant fusiform aneurysm of the pericallosal artery with «hemi-bonnet bypass¼ procedure (case report and literature review)]. / Vyklyuchenie gigantskoi fuziformnoi anevrizmy perikalleznoi arterii s primeneniem obkhodnogo shuntirovaniya po tipu «hemi-bonnet bypass¼. Sluchai iz praktiki i obzor literatury.

A 30-year-old woman with giant fusiform aneurysm of the azygos anterior cerebral artery is reported. Clipping of the aneurysm followed by modeling of pericallosal artery was performed in 2017. However, further enlargement of the aneurysm has been observed for subsequent 2 years. The patient underwent redo surgery with excision of the aneurysm followed by «hemi-bonnet bypass¼ procedure (anastomosis between superficial temporal artery and anterior cerebral artery with radial artery as an interposition graft). Literature data on reconstructive surgery in the treatment of complex pericallosal artery aneurysms are reviewed.

101 Dothideomycetes genomes: A test case for predicting lifestyles and emergence of pathogens.

Dothideomycetes is the largest class of kingdom Fungi and comprises an incredible diversity of lifestyles, many of which have evolved multiple times. Plant pathogens represent a major ecological niche of the class Dothideomycetes and they are known to infect most major food crops and feedstocks for biomass and biofuel production. Studying the ecology and evolution of Dothideomycetes has significant implications for our fundamental understanding of fungal evolution, their adaptation to stress and host specificity, and practical implications with regard to the effects of climate change and on the food, feed, and livestock elements of the agro-economy. In this study, we present the first large-scale, whole-genome comparison of 101 Dothideomycetes introducing 55 newly sequenced species. The availability of whole-genome data produced a high-confidence phylogeny leading to reclassification of 25 organisms, provided a clearer picture of the relationships among the various families, and indicated that pathogenicity evolved multiple times within this class. We also identified gene family expansions and contractions across the Dothideomycetes phylogeny linked to ecological niches providing insights into genome evolution and adaptation across this group. Using machine-learning methods we classified fungi into lifestyle classes with >95 % accuracy and identified a small number of gene families that positively correlated with these distinctions. This can become a valuable tool for genome-based prediction of species lifestyle, especially for rarely seen and poorly studied species.

[Use of the 'bonnet' bypass in treating a patient with symptomatic occlusion of the ipsilateral carotid arteries. Clinical observation]. / Ispol'zovanie 'bonnet' bypass u patsienta s simptomnoi okkliuziei ipsilateral'nykh sonnykh arterii. Klinicheskoe nabliudenie.

In this article we present the clinical case of 63 y.o. man with chronic occlusion of the right common, internal, and external carotid arteries, and critical stenosis of the left internal carotid artery, with complaints of muscle weakness and decreased sensitivity of the left limbs. The patient underwent a staged brain revascularization, the left carotid endarterectomy was performed at the first stage and followed by bonnet bypass, which consists in anastomosing the contralateral superficial temporal artery with the ipsilateral intracranial artery by autograft interposition. In the postoperative period, the patient's neurological symptoms regressed. This case demonstrates the possibility of using bonnet bypass as an alternative revascularization method in patients with cerebral blood circulation insufficiency.

The gold-standard genome of Aspergillus niger NRRL 3 enables a detailed view of the diversity of sugar catabolism in fungi.

The fungal kingdom is too large to be discovered exclusively by classical genetics. The access to omics data opens a new opportunity to study the diversity within the fungal kingdom and how adaptation to new environments shapes fungal metabolism. Genomes are the foundation of modern science but their quality is crucial when analysing omics data. In this study, we demonstrate how one gold-standard genome can improve functional prediction across closely related species to be able to identify key enzymes, reactions and pathways with the focus on primary carbon metabolism. Based on this approach we identified alternative genes encoding various steps of the different sugar catabolic pathways, and as such provided leads for functional studies into this topic. We also revealed significant diversity with respect to genome content, although this did not always correlate to the ability of the species to use the corresponding sugar as a carbon source.

Genomic and exoproteomic diversity in plant biomass degradation approaches among Aspergilli.

We classified the genes encoding carbohydrate-active enzymes (CAZymes) in 17 sequenced genomes representing 16 evolutionarily diverse Aspergillus species. We performed a phylogenetic analysis of the encoding enzymes, along with experimentally characterized CAZymes, to assign molecular function to the Aspergilli CAZyme families and subfamilies. Genome content analysis revealed that the numbers of CAZy genes per CAZy family related to plant biomass degradation follow closely the taxonomic distance between the species. On the other hand, growth analysis showed almost no correlation between the number of CAZyme genes and the efficiency in polysaccharide utilization. The exception is A. clavatus where a reduced number of pectinolytic enzymes can be correlated with poor growth on pectin. To gain detailed information on the enzymes used by Aspergilli to breakdown complex biomass, we conducted exoproteome analysis by mass spectrometry. These results showed that Aspergilli produce many different enzymes mixtures in the presence of sugar beet pulp and wheat bran. Despite the diverse enzyme mixtures produced, species of section Nigri, A. aculeatus, A. nidulans and A. terreus, produce mixtures of enzymes with activities that are capable of digesting all the major polysaccharides in the available substrates, suggesting that they are capable of degrading all the polysaccharides present simultaneously. For the other Aspergilli, typically the enzymes produced are targeted to a subset of polysaccharides present, suggesting that they can digest only a subset of polysaccharides at a given time.

The fungus that came in from the cold: dry rot's pre-adapted ability to invade buildings.

Many organisms benefit from being pre-adapted to niches shaped by human activity, and have successfully invaded man-made habitats. One such species is the dry rot fungus Serpula lacrymans, which has a wide distribution in buildings in temperate and boreal regions, where it decomposes coniferous construction wood. Comparative genomic analyses and growth experiments using this species and its wild relatives revealed that S. lacrymans evolved a very effective brown rot decay compared to its wild relatives, enabling an extremely rapid decay in buildings under suitable conditions. Adaptations in intracellular transport machineries promoting hyphal growth, and nutrient and water transport may explain why it is has become a successful invader of timber in houses. Further, we demonstrate that S. lacrymans has poor combative ability in our experimental setup, compared to other brown rot fungi. In sheltered indoor conditions, the dry rot fungus may have limited encounters with other wood decay fungi compared to its wild relatives. Overall, our analyses indicate that the dry rot fungus is an ecological specialist with poor combative ability against other fungi.

Protein content of human saliva in various psycho-emotional states.

The protein composition of human saliva depends on psycho-emotional state of individuals. Depression was accompanied by decrease of proteins of molecular masses ranging from 20 to 200 kD, whereas emotionally positive intellectual activity caused the opposite effect. It is suggested that human saliva may be used as an experimental model for the development of diagnostics of various psycho-physiological states.

Detection of protein fold similarity based on correlation of amino acid properties.

An increasing number of proteins with weak sequence similarity have been found to assume similar three-dimensional fold and often have similar or related biochemical or biophysical functions. We propose a method for detecting the fold similarity between two proteins with low sequence similarity based on their amino acid properties alone. The method, the proximity correlation matrix (PCM) method, is built on the observation that the physical properties of neighboring amino acid residues in sequence at structurally equivalent positions of two proteins of similar fold are often correlated even when amino acid sequences are different. The hydrophobicity is shown to be the most strongly correlated property for all protein fold classes. The PCM method was tested on 420 proteins belonging to 64 different known folds, each having at least three proteins with little sequence similarity. The method was able to detect fold similarities for 40% of the 420 sequences. Compared with sequence comparison and several fold-recognition methods, the method demonstrates good performance in detecting fold similarities among the proteins with low sequence identity. Applied to the complete genome of Methanococcus jannaschii, the method recognized the folds for 22 hypothetical proteins.

Simulated annealing for alpha-helical protein folding: searches in vicinity of the "molten globule" state.

A new model for simulation of protein folding of alpha-helical proteins with known secondary structure is proposed. We are dealing here with the analysis of alpha-helix packings rather than with a detailed atom structure of a whole protein. Starting from a random compact packing of the helices the search is focused on a vicinity of "molten globule" states of a protein. In contrast to the majority of the known approaches for estimation of a protein free energy we introduce a simplified potential of interactions with solvent and consider conformational energy of the loops in addition to mean-force potential. The model was applied to several globular alpha-helical proteins and demonstrated high prediction accuracy in comparison with other known models.

Interhelical contacts determining the architecture of alpha-helical globular proteins.

An approach based on a presentation of alpha-helical protein topology as a graph is presented. The approach allows to estimate a role of each interhelical contact in the whole protein topology and to classify the contacts. It is shown that a consideration of only about a half of the whole pool of interhelical contacts exposed in the protein is enough for a determination of protein architecture. Such contacts are called as major and their quantitative characteristics are obtained. Moreover, providing a clear and simple presentation of the protein topology, the approach can be applied for a description of structural domain/subdomain arrangement of alpha-helical proteins and illustration of their folding/denaturation paths.