Impacts of urban emissions and air quality in São Paulo State, Brazil.

Daily violations of air quality have an impact on urban populations and cause damage to the environment. Thus, the study evaluated the violations of the daily concentrations of SO2, NO2, and PM10, in regions of the State of São Paulo (SSP), based on the National Environment Council (CONAMA) resolution no 491/2018 and the World Health Organization (WHO - World Health Organization. (2016). Ambient air pollution: a global assessment of exposure and burden of disease.) criteria. Daily SO2, NO2, and PM10data from 6 air quality stations operated by Environmental Company of the State of São Paulo CETESB (1996-2011) were organized and submitted to quality control, with data faults (gaps) being identified. The imputation of data via spline proved satisfactory in filling in the gaps (r > 0.7 and low values of Standard Error of the Estimate (SEE) and Root Mean Square Error (RMSE). The cluster analysis (CA) applied to SO2 formed only one homogeneous group (G1). Contrariwise, NO2 and PM10 formed two homogeneous groups (G1 and G2) each. The stations that showed the greatest similarity according to the CA were Cerqueira Cesar and Osasco. The cophenetic matrix generated for SO2 (0.83), NO2 (0.79), and PM10 (0.77) indicate a satisfactory adjustment of the dendrograms. The exploratory statistics applied to groups G1 and G2 point to the high variability of outliers. The WHO criteria are more restrictive than CONAMA regarding daily violations, with a reduction in SO2 and an increase in specific years for NO2 and PM10. Such variability is due to the adoption of public policies by the SSP and the influence of meteorological systems, being confirmed by the Run test that indicated oscillations in the time series, mainly in PM10, and also recognized well-defined biannual cycles.

The Hows of Resident-Driven Community Empowerment toward Health Equity.

BACKGROUND: This article details community engagement, design, and implementation strategies for the Raices-Xidid-Roots (RXR) Academy. RXR provided a linguistically accessible and culturally relevant curriculum to residents of Spanish and Somali-speaking immigrant, asylee, and refugee backgrounds. OBJECTIVES: This study examined the implementation of the RXR program, including participation and adjustments needed to foster participant engagement and active voice, and explored participant actions to address self-identified aspirations as part of participation. RXR's goal was to empower Morgan County, Colorado, Spanish- and Somalispeaking cohorts of residents from immigrant, asylee, and refugee backgrounds such that they could autonomously plan, create, and sustain programs and organizations to meet their community needs. METHODS: The observational study design included process and implementation evaluative approaches, including interview, project team meeting debriefings, and course organizer reflections, to identify and address implementation challenges, learn how the program met participants' needs, and understand keys to maintaining participant engagement. RESULTS: Cultural adaptation of the content was key to maintaining consistent participant engagement, including delivering programming in participant preferred languages and tailoring curriculum to participant cultural practices. Participants indicated that language barriers had previously prevented them from accessing the content provided by the program's curriculum. Adaptations included adjusting meeting logistics, participant compensation, and unit timing. The Two RXR Academy cohorts developed initiatives that addressed community-identified needs. LESSONS LEARNED: Three RXR design elements supported participant engagement and development of community power: 1) language access beyond the language justice model by providing programming in the participants' preferred language, 2) cultural adaptation of programming, and 3) community ownership and active voiceConclusions: The RXR program provided opportunities for skill development among Morgan County's non-native English-speaking residents and led to the design and implementation of resident-driven projects.

"It depends:" a qualitative study on digital health academic-industry collaboration.

BACKGROUND: Academic-industry collaborations (AICs) are endorsed to alleviate challenges in digital health, but partnership experiences remain understudied. The qualitative study's objective investigated collaboration experiences between academic institutions and digital health companies. METHODS: A phenomenology methodology captured experiences of AICs, eliciting perspectives from academic researchers and industry affiliates (e.g., leadership, company investigators). Semi-structured interviews probed eligible collaborators about their experiences in digital health. Analysts coded and organized data into significant statements reaching thematic saturation. RESULTS: Participants (N=20) were interviewed from 6 academic institutions and 14 unique industry partners. Seven themes emerged: (I) Collaboration evolves with time, relationships, funding, and evidence; (II) Collaboration demands strong relationships and interpersonal dynamics; (III) Operational processes vary across collaborations; (IV) Collaboration climate and context matters; (V) Shared expectations lead to a better understanding of success; (VI) Overcoming challenges with recommendations; (VII) Collaboration may help navigate the global pandemic. CONCLUSIONS: Digital health academic industry collaboration demands strong relationships, requiring flexible mechanisms of collaboration and cultural fit. Diverse models of collaboration exist and remain dependent on contextual factors. While no collaboration conquers all challenges in digital health, AICs may serve as a facilitator for improved digital health products, thus advancing science, promoting public health, and benefiting the economy.

Fire foci dynamics and their relationship with socioenvironmental factors and meteorological systems in the state of Alagoas, Northeast Brazil.

The objective is to evaluate the fire foci dynamics via environmental satellites and their relationship with socioenvironmental factors and meteorological systems in the state of Alagoas, Brazil. Data considered the period between 2000 and 2017 and was obtained from CPTEC/INPE. Annual and monthly analyzes were performed based on descriptive, exploratory (boxplot) and multivariate statistics analyzes (cluster analysis (CA), principal component analysis (PCA)) and Poisson regression models (based on 2000 and 2010 census data). CA based on the Ward method identified five fire foci homogeneous groups (G1 to G5), while Coruripe did not classify within any group (NA); therefore, the CA technique was consistent (CCC = 0.772). Group G1 is found in all regions of Alagoas, while G2, G5, and NA groups are found in Baixo São Francisco, Litoral, and Zona da Mata regions. Most fire foci were observed in the Litoral region. Seasonally, the largest records were from October to December months for all groups, influenced by the sugarcane harvesting period. The G4 group and Coruripe accounted for 60,767 foci (32.1%). The highest number of fire foci occurred in 2012 and 2015 (between 8000 and 9000 foci), caused by the action of the El Niño-Southern Oscillation. The Poisson regression showed that the dynamics of fire foci are directly associated with the Gini index and Human Development Index (models 1 and 3). Based on the PCA, the three components captured 78.8% of the total variance explained, and they were strongly influenced by the variables: population, GDP, and demographic density. The municipality of Maceió has the largest contribution from the fire foci, with values higher than 40%, and in PC1 and PC2 are related to urban densification and population growth.

Amazonian deforestation and soil biodiversity.

Clearance and perturbation of Amazonian forests are one of the greatest threats to tropical biodiversity conservation of our times. A better understanding of how soil communities respond to Amazonian deforestation is crucially needed to inform policy interventions that effectively protect biodiversity and the essential ecosystem services it provides. We assessed the impact of deforestation and ecosystem conversion to arable land on Amazonian soil biodiversity through a meta-analysis. We analyzed 274 pairwise comparisons of soil biodiversity in Amazonian primary forests and sites under different stages of deforestation and land-use conversion: disturbed (wildfire and selective logging) and slash-and-burnt forests, pastures, and cropping systems. Overall, 60% and 51% of responses of soil macrofauna and microbial community attributes (i.e., abundance, biomass, richness, and diversity indexes) to deforestation were negative, respectively. We found few studies on mesofauna (e.g., microarthropods) and microfauna (e.g., protozoa and nematodes), so those groups could not be analyzed. Macrofauna abundance and biomass were more vulnerable to the displacement of forests by pastures than by agricultural fields, whereas microbes showed the opposite pattern. Effects of Amazonian deforestation on macrofauna were more detrimental at sites with mean annual precipitation >1900 mm, and higher losses of microbes occurred in highly acidic soils (pH < 4.5). Limited geographic coverage, omission of meso- and microfauna, and low taxonomic resolution were main factors impairing generalizations from the data set. Few studies assessed the impacts of within-forest disturbance (wildfires and selective logging) on soil species in Amazonia, where logging operations rapidly expand across public lands and more frequent severe dry seasons are increasing the prevalence of wildfires.

Deforestación en el Amazonas y Biodiversidad del Suelo Resumen Actualmente, el despeje y la perturbación de los bosques del Amazonas son las principales amenazas para la conservación de la biodiversidad tropical. Se requiere urgentemente de un mejor entendimiento sobre cómo las comunidades del suelo responden a la deforestación amazónica para informar a las intervenciones políticas que protegen efectivamente a la biodiversidad y a los servicios ambientales esenciales que proporciona. Evaluamos el impacto de la deforestación y la conversión del ecosistema a suelo arable sobre la biodiversidad del suelo amazónico por medio de un meta-análisis. Analizamos 274 comparaciones por pares de la biodiversidad del suelo amazónico en bosques primarios y sitios bajo diferentes etapas de deforestación y conversión de uso de suelo: bosques perturbados (incendios forestales y tala selectiva) y de corte-y-quema, pasturas, y sistemas agrícolas. En general, el 60% y el 51% de las respuestas de los atributos (es decir, abundancia, biomasa, riqueza, e índices de biodiversidad) de la macrofauna del suelo y de las comunidades microbianas ante la deforestación fueron negativas, respectivamente. Encontramos pocos estudios sobre la mesofauna (p. ej.: microartrópodos) y la microfauna (p. ej.: protozoarios y nematodos), así que estos grupos no pudieron ser analizados. La abundancia de la macrofauna y la biomasa fueron más vulnerables al desplazamiento de bosques por las pasturas que por los campos agrícolas, mientras que los microbios mostraron el patrón opuesto. Los efectos de la deforestación amazónica sobre la macrofauna fueron más dañinos en sitios con una precipitación anual media mayor a los 1,900 mm, y ocurrieron pérdidas más elevadas de microbios en suelos con una acidez alta (pH < 4.5). La cobertura geográfica limitada, la omisión de la mesofauna y la microfauna, y la baja resolución taxonómica fueron los factores principales que obstaculizaron las generalizaciones del conjunto de datos. Pocos estudios evaluaron los impactos de las perturbaciones internas del bosque (incendios forestales y tala selectiva) sobre las especies del suelo amazónico, a la vez que las operaciones de tala se expanden rápidamente en los terrenos públicos y la ocurrencia con mayor frecuencia de temporadas con sequía grave aumentan la prevalencia de los incendios forestales.

RNA-Rocket: an RNA-Seq analysis resource for infectious disease research.

MOTIVATION: RNA-Seq is a method for profiling transcription using high-throughput sequencing and is an important component of many research projects that wish to study transcript isoforms, condition specific expression and transcriptional structure. The methods, tools and technologies used to perform RNA-Seq analysis continue to change, creating a bioinformatics challenge for researchers who wish to exploit these data. Resources that bring together genomic data, analysis tools, educational material and computational infrastructure can minimize the overhead required of life science researchers. RESULTS: RNA-Rocket is a free service that provides access to RNA-Seq and ChIP-Seq analysis tools for studying infectious diseases. The site makes available thousands of pre-indexed genomes, their annotations and the ability to stream results to the bioinformatics resources VectorBase, EuPathDB and PATRIC. The site also provides a combination of experimental data and metadata, examples of pre-computed analysis, step-by-step guides and a user interface designed to enable both novice and experienced users of RNA-Seq data. AVAILABILITY AND IMPLEMENTATION: RNA-Rocket is available at rnaseq.pathogenportal.org. Source code for this project can be found at github.com/cidvbi/PathogenPortal. CONTACT: anwarren@vt.edu SUPPLEMENTARY INFORMATION: Supplementary materials are available at Bioinformatics online.

Curation, integration and visualization of bacterial virulence factors in PATRIC.

MOTIVATION: We've developed a highly curated bacterial virulence factor (VF) library in PATRIC (Pathosystems Resource Integration Center, www.patricbrc.org) to support infectious disease research. Although several VF databases are available, there is still a need to incorporate new knowledge found in published experimental evidence and integrate these data with other information known for these specific VF genes, including genomic and other omics data. This integration supports the identification of VFs, comparative studies and hypothesis generation, which facilitates the understanding of virulence and pathogenicity. RESULTS: We have manually curated VFs from six prioritized NIAID (National Institute of Allergy and Infectious Diseases) category A-C bacterial pathogen genera, Mycobacterium, Salmonella, Escherichia, Shigella, Listeria and Bartonella, using published literature. This curated information on virulence has been integrated with data from genomic functional annotations, trancriptomic experiments, protein-protein interactions and disease information already present in PATRIC. Such integration gives researchers access to a broad array of information about these individual genes, and also to a suite of tools to perform comparative genomic and transcriptomics analysis that are available at PATRIC. AVAILABILITY AND IMPLEMENTATION: All tools and data are freely available at PATRIC (http://patricbrc.org). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Comparative nutritional and chemical phenome of Clostridium difficile isolates determined using phenotype microarrays.

OBJECTIVES: Clostridium difficile infection (CDI) is the leading cause of infectious diarrhea in North America and Europe. The risk of CDI increases significantly in the case where antimicrobial treatment reduces the number of competing bacteria in the gut, thus leading to the increased availability of nutrients and loss of colonization resistance. The objective of this study was to determine comprehensive nutritional utilization and the chemical sensitivity profile of historic and newer C. difficile isolates and to examine the possible role of the phenotype diversity in C. difficile virulence. METHODS: Phenotype microarrays (PMs) were used to elucidate the complete nutritional and chemical sensitivity profile of six C. difficile isolates. RESULTS: Of the 760 nutrient sources tested, 285 compounds were utilized by at least one strain. Among the C. difficile isolates compared, R20291, a recent hypervirulent outbreak-associated strain, appears to have an expanded nutrient utilization profile when compared to all other strains. CONCLUSIONS: The expanded nutritional utilization profile of some newer C. difficile strains could be one of the reasons for infections in patients who are not exposed to the hospital environment or not undergoing antibiotic treatment. This nutritional profile could be used to design tube feeding formulas that reduce the risk of CDI.

Comparative genomic analysis at the PATRIC, a bioinformatic resource center.

The Pathosystems Resource Integration Center (PATRIC) is a genomics-centric relational database and bioinformatics resource designed to assist scientists in infectious-disease research. This method paper provides detailed instructions on using this resource to finding data specific to genomes, saving it in a personalized workspace and using a variety of interactive tools to analyze that data. While PATRIC contains many diverse tools and functionalities to explore both genome-scale and gene expression data, the main focus of this chapter is on comparative analysis of bacterial genomes.

Standardized metadata for human pathogen/vector genomic sequences.

High throughput sequencing has accelerated the determination of genome sequences for thousands of human infectious disease pathogens and dozens of their vectors. The scale and scope of these data are enabling genotype-phenotype association studies to identify genetic determinants of pathogen virulence and drug/insecticide resistance, and phylogenetic studies to track the origin and spread of disease outbreaks. To maximize the utility of genomic sequences for these purposes, it is essential that metadata about the pathogen/vector isolate characteristics be collected and made available in organized, clear, and consistent formats. Here we report the development of the GSCID/BRC Project and Sample Application Standard, developed by representatives of the Genome Sequencing Centers for Infectious Diseases (GSCIDs), the Bioinformatics Resource Centers (BRCs) for Infectious Diseases, and the U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), informed by interactions with numerous collaborating scientists. It includes mapping to terms from other data standards initiatives, including the Genomic Standards Consortium's minimal information (MIxS) and NCBI's BioSample/BioProjects checklists and the Ontology for Biomedical Investigations (OBI). The standard includes data fields about characteristics of the organism or environmental source of the specimen, spatial-temporal information about the specimen isolation event, phenotypic characteristics of the pathogen/vector isolated, and project leadership and support. By modeling metadata fields into an ontology-based semantic framework and reusing existing ontologies and minimum information checklists, the application standard can be extended to support additional project-specific data fields and integrated with other data represented with comparable standards. The use of this metadata standard by all ongoing and future GSCID sequencing projects will provide a consistent representation of these data in the BRC resources and other repositories that leverage these data, allowing investigators to identify relevant genomic sequences and perform comparative genomics analyses that are both statistically meaningful and biologically relevant.

Comparative phylogenomics and evolution of the Brucellae reveal a path to virulence.

Brucella species include important zoonotic pathogens that have a substantial impact on both agriculture and human health throughout the world. Brucellae are thought of as "stealth pathogens" that escape recognition by the host innate immune response, modulate the acquired immune response, and evade intracellular destruction. We analyzed the genome sequences of members of the family Brucellaceae to assess its evolutionary history from likely free-living soil-based progenitors into highly successful intracellular pathogens. Phylogenetic analysis split the genus into two groups: recently identified and early-dividing "atypical" strains and a highly conserved "classical" core clade containing the major pathogenic species. Lateral gene transfer events brought unique genomic regions into Brucella that differentiated them from Ochrobactrum and allowed the stepwise acquisition of virulence factors that include a type IV secretion system, a perosamine-based O antigen, and systems for sequestering metal ions that are absent in progenitors. Subsequent radiation within the core Brucella resulted in lineages that appear to have evolved within their preferred mammalian hosts, restricting their virulence to become stealth pathogens capable of causing long-term chronic infections.

PATRIC, the bacterial bioinformatics database and analysis resource.

The Pathosystems Resource Integration Center (PATRIC) is the all-bacterial Bioinformatics Resource Center (BRC) (http://www.patricbrc.org). A joint effort by two of the original National Institute of Allergy and Infectious Diseases-funded BRCs, PATRIC provides researchers with an online resource that stores and integrates a variety of data types [e.g. genomics, transcriptomics, protein-protein interactions (PPIs), three-dimensional protein structures and sequence typing data] and associated metadata. Datatypes are summarized for individual genomes and across taxonomic levels. All genomes in PATRIC, currently more than 10,000, are consistently annotated using RAST, the Rapid Annotations using Subsystems Technology. Summaries of different data types are also provided for individual genes, where comparisons of different annotations are available, and also include available transcriptomic data. PATRIC provides a variety of ways for researchers to find data of interest and a private workspace where they can store both genomic and gene associations, and their own private data. Both private and public data can be analyzed together using a suite of tools to perform comparative genomic or transcriptomic analysis. PATRIC also includes integrated information related to disease and PPIs. All the data and integrated analysis and visualization tools are freely available. This manuscript describes updates to the PATRIC since its initial report in the 2007 NAR Database Issue.

Consensus statement understanding health and malnutrition through a systems approach: the ENOUGH program for early life.

Nutrition research, like most biomedical disciplines, adopted and often uses experimental approaches based on Beadle and Tatum's one gene-one polypeptide hypothesis, thereby reducing biological processes to single reactions or pathways. Systems thinking is needed to understand the complexity of health and disease processes requiring measurements of physiological processes, as well as environmental and social factors, which may alter the expression of genetic information. Analysis of physiological processes with omics technologies to assess systems' responses has only become available over the past decade and remains costly. Studies of environmental and social conditions known to alter health are often not connected to biomedical research. While these facts are widely accepted, developing and conducting comprehensive research programs for health are often beyond financial and human resources of single research groups. We propose a new research program on essential nutrients for optimal underpinning of growth and health (ENOUGH) that will use systems approaches with more comprehensive measurements and biostatistical analysis of the many biological and environmental factors that influence undernutrition. Creating a knowledge base for nutrition and health is a necessary first step toward developing solutions targeted to different populations in diverse social and physical environments for the two billion undernourished people in developed and developing economies.

Differential stress transcriptome landscape of historic and recently emerged hypervirulent strains of Clostridium difficile strains determined using RNA-seq.

C. difficile is the most common cause of nosocomial diarrhea in North America and Europe. Genomes of individual strains of C. difficile are highly divergent. To determine how divergent strains respond to environmental changes, the transcriptomes of two historic and two recently isolated hypervirulent strains were analyzed following nutrient shift and osmotic shock. Illumina based RNA-seq was used to sequence these transcriptomes. Our results reveal that although C. difficile strains contain a large number of shared and strain specific genes, the majority of the differentially expressed genes were core genes. We also detected a number of transcriptionally active regions that were not part of the primary genome annotation. Some of these are likely to be small regulatory RNAs.

The condition-dependent transcriptional landscape of Burkholderia pseudomallei.

Burkholderia pseudomallei (Bp), the causative agent of the often-deadly infectious disease melioidosis, contains one of the largest prokaryotic genomes sequenced to date, at 7.2 Mb with two large circular chromosomes (1 and 2). To comprehensively delineate the Bp transcriptome, we integrated whole-genome tiling array expression data of Bp exposed to >80 diverse physical, chemical, and biological conditions. Our results provide direct experimental support for the strand-specific expression of 5,467 Sanger protein-coding genes, 1,041 operons, and 766 non-coding RNAs. A large proportion of these transcripts displayed condition-dependent expression, consistent with them playing functional roles. The two Bp chromosomes exhibited dramatically different transcriptional landscapes--Chr 1 genes were highly and constitutively expressed, while Chr 2 genes exhibited mosaic expression where distinct subsets were expressed in a strongly condition-dependent manner. We identified dozens of cis-regulatory motifs associated with specific condition-dependent expression programs, and used the condition compendium to elucidate key biological processes associated with two complex pathogen phenotypes--quorum sensing and in vivo infection. Our results demonstrate the utility of a Bp condition-compendium as a community resource for biological discovery. Moreover, the observation that significant portions of the Bp virulence machinery can be activated by specific in vitro cues provides insights into Bp's capacity as an "accidental pathogen", where genetic pathways used by the bacterium to survive in environmental niches may have also facilitated its ability to colonize human hosts.

Bacterial DNA sifted from the Trichoplax adhaerens (Animalia: Placozoa) genome project reveals a putative rickettsial endosymbiont.

Eukaryotic genome sequencing projects often yield bacterial DNA sequences, data typically considered as microbial contamination. However, these sequences may also indicate either symbiont genes or lateral gene transfer (LGT) to host genomes. These bacterial sequences can provide clues about eukaryote-microbe interactions. Here, we used the genome of the primitive animal Trichoplax adhaerens (Metazoa: Placozoa), which is known to harbor an uncharacterized Gram-negative endosymbiont, to search for the presence of bacterial DNA sequences. Bioinformatic and phylogenomic analyses of extracted data from the genome assembly (181 bacterial coding sequences [CDS]) and trace read archive (16S rDNA) revealed a dominant proteobacterial profile strongly skewed to Rickettsiales (Alphaproteobacteria) genomes. By way of phylogenetic analysis of 16S rDNA and 113 proteins conserved across proteobacterial genomes, as well as identification of 27 rickettsial signature genes, we propose a Rickettsiales endosymbiont of T. adhaerens (RETA). The majority (93%) of the identified bacterial CDS belongs to small scaffolds containing prokaryotic-like genes; however, 12 CDS were identified on large scaffolds comprised of eukaryotic-like genes, suggesting that T. adhaerens might have recently acquired bacterial genes. These putative LGTs may coincide with the placozoan's aquatic niche and symbiosis with RETA. This work underscores the rich, and relatively untapped, resource of eukaryotic genome projects for harboring data pertinent to host-microbial interactions. The nature of unknown (or poorly characterized) bacterial species may only emerge via analysis of host genome sequencing projects, particularly if these species are resistant to cell culturing, as are many obligate intracellular microbes. Our work provides methodological insight for such an approach.

Proteomic comparison of historic and recently emerged hypervirulent Clostridium difficile strains.

Clostridium difficile in recent years has undergone rapid evolution and has emerged as a serious human pathogen. Proteomic approaches can improve the understanding of the diversity of this important pathogen, especially in comparing the adaptive ability of different C. difficile strains. In this study, TMT labeling and nanoLC-MS/MS driven proteomics were used to investigate the responses of four C. difficile strains to nutrient shift and osmotic shock. We detected 126 and 67 differentially expressed proteins in at least one strain under nutrition shift and osmotic shock, respectively. During nutrient shift, several components of the phosphotransferase system (PTS) were found to be differentially expressed, which indicated that the carbon catabolite repression (CCR) was relieved to allow the expression of enzymes and transporters responsible for the utilization of alternate carbon sources. Some classical osmotic shock associated proteins, such as GroEL, RecA, CspG, and CspF, and other stress proteins such as PurG and SerA were detected during osmotic shock. Furthermore, the recently emerged strains were found to contain a more robust gene network in response to both stress conditions. This work represents the first comparative proteomic analysis of historic and recently emerged hypervirulent C. difficile strains, complementing the previously published proteomics studies utilizing only one reference strain.

Functional assignment of Mycobacterium tuberculosis proteome revealed by genome-scale fold-recognition.

Hundreds of putative enzymes from Mycobacterium tuberculosis as well as other mycobacteria remain categorized as "conserved hypothetical proteins" or "hypothetical proteins", offering little or no information on their functional role in pathogenic and non-pathogenic processes. In this study we have predicted the fold and 3-D structure of more than 99% of all proteins encoded in the genome of M. tuberculosis H37Rv. Fold-recognition, database search, 3-D modelling was performed using Protein Homology/analogy Recognition Engine V 2.0 (Phyre2). These results are used to tentatively assign potential function for unannotated enzymes and proteins. In summary, fold-recognition and structural homology might be used as a complementary tool in genome annotation efforts and furthermore, it can deliver primary sequence-independent information regarding structure, ligands and even substrate specificity for enzymes that display low primary sequence identity with potential homologues in other species.