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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - OPATHY (From Omics to Patient: Improving Diagnostics of Pathogenic Yeasts)

Teaser

Summary

OPATHY was an innovative translational research training network that explored the potential of omics technologies, including genomics, transcriptomics and proteomics, to study the interactions of yeasts that cause disease to humans (e.g. Candida and Cryptococcus sp.) with the host, and to develop new diagnostic tools to monitor yeast infections in the clinic. Today, these infections are poorly understood, difficult to diagnose, and are becoming increasingly frequent and serious, affecting over 300 million people worldwide. OPATHY has exploited omics technologies to investigate host-pathogen interactions during yeast infection and colonization with a primary focus on their potential to develop innovative diagnostics tools to improve health care. For this, proteomics, transcriptomics and genomics measurements of strains and infections were integrated with state of the art computational analyses to identify novel biomarkers able to determine the infection stage, the infective pathogen, and the potential resistance traits. This knowledge is driving the development of diagnostic tools based on the detection of specific DNA sequences (by PCR) or antibodies (by Elisa or proteomics). Conclusions: Integration of omics technologies by OPATHY experts have advanced our knowledge on fungal yeast infections and have identified novel biomarkers that are now driving the development of innovative diagnostic tools.

Work performed

The project ended on the 31st of August 2019 and all ESRs are in the process of finishing their PhD, finalizing their last articles and searching for the next step in their careers. The project has resulted already in over 25 peer-reviewed publications co-authored by ESRs of this network, including a review entitled â€œRecent trends in molecular diagnostics of yeast infections: from PCR to NGS.â€ published in the prestigious journal FEMS Microbiology Reviews and jointly written by all consortium members. The project has ensured coordination through a summer meeting and a winter course each year as well as a bi-weekly virtual meeting in which ESRs sequentially presented their results. The consortium has also participated in several science communication activities and produced a cartoon science communication video that reached over 6000 views in less than four months (the beast in yeast https://www.youtube.com/watch?v=HsxwZcJ8fJg). Most importantly, the main scientific aims of the project have been largely accomplished.

The specific scientific and technical objectives for the project are:
1. Study the genomic, transcriptomic and proteomic diversity of yeast pathogens, focusing on the discovery of specific biomarkers with diagnostic potential.
2. Advance our understanding of the dynamics of host-pathogen interactions during the course of infection and colonization and how this varies across species.
3. Develop novel analysis tools that exploit recently developed high-throughput (-omics) techniques and that enable faster and more efficient diagnostics of fungal pathogens, resistance traits, and infection stages.

With respect to objective 1. (Study the genomic, transcriptomic and proteomic diversity of yeast pathogens, focusing on the discovery of specific biomarkers with diagnostic potential.). The different work packages have obtained a) whole genome sequences b) transcriptomic profiling of host-pathogen interactions, and c) proteomics surveys from which candidate biomarkers have been prioritized for further development. A protein antibody for one such biomarkes have resulted in a filed patent, and several multiplex systems to detect several DNA-based biomarkers are currently being developed.

With respect to objective 2: A first time-course experiment has been successfully performed, in which the transcriptomes from both the host and the pathogen are traced and provide a detailed view of host-pathogen interactions. A manuscript is in preparation.

Objective 3 heavily relied on the above ones. Several computational tools and databases to ease the processing, analysis and interpretation of diverse types of omics data have been developed, including Candidamine (www.candidamine.org) focused on Omics-related data for the main Candida pathogens. Several potential novel diagnostic tools, derived from investigations within OPATHY have been explored and some of them are advancing towards patenting, valorization, and validation in the clinical settings. As indicated above a patent has been filed and several other diagnostic markers are being explored in the clinical setting.

The main results of the project are:

â€“ A cartography of genomic, transcriptomic and proteomic resources have been produced for the main Candida pathogens, as well as for some rare (emerging species). This resource has been mined for the finding of novel diagnostic markers and has been put available for the whole community through http://candidamine.org database.

- Several new tools have been developed in the framework of this project which have been made available to the community, these include new proteomics based test for anti-fungal resistance (MBT-ASTRA), specific multiplex PCR probes for detecting different Candida species, as well as several bioinfomatics pipelines and tools for genome, transcriptome, and proteome analysis. These have been published in peer-reviewed journals and bioinformatics tools have been made accessible to the research communi

Final results

The tools developed in OPATHY will be validated in a clinical study of key patient cohorts. The participation of two clinical centres and four companies is of paramount importance for the network to provide an integrative and transversal research and training environment and will be key for translating the key discoveries to the everyday practice in the clinic. Importantly, the methodologies and approaches of OPATHY can be easily extended to the study and identification of other human, animal and plant microbial pathogens, or the tracing of relevant industrial organisms. Grounded on solid individual research projects, OPATHY has trained Early Stage Researchers in several scientific technologies and fields and transferable skills, to boost their careers as innovative and creative researchers. These ESRs are now in the process of finishing their PhD and finding their next step in their careers, at least two ESRs have been already invited for postdoctoral research positions upon completion of their PhDs, some ESRs are considering careers in Industry in fields related to the topic of their PhD.

Through its many communication actions OPATHY has contributed to increase the awareness on fungal diseases and on the research that is needed to combat them. The many scientific findings published and the methods developed by the consortium that are already available are already contributing to accelerate the research in fungal diseases. Finally, some of the biomarkers identified are proceeding to further stages of developments into tools or kits that will likely have an impact in the clinics, thereby helping to improve the lives of people suffering from fungal infections.