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Innovative training in methods for future data

Periodic Reporting for period 2 - IMforFUTURE (Innovative training in methods for future data)

Berichtszeitraum: 2019-04-01 bis 2021-07-31

IMforFUTURE (Innovative Training in Methods for Future Data) is an innovative multidisciplinary and intersectoral research training programme that addresses current shortcomings in omics research. We aim to open a new research horizon in integration of genetic, glycomic, and epigenomic datasets into systems biology by developing innovative methods for the generation of omics measurements and for integrative analysis of omics data. Our multidisciplinary approach – from measuring data, via data analysis to interpretation or results – provides a unique training environment for our ESRs who will need to be able to act as bridge between several diverse disciplines to significantly contribute to the analysis of future datasets in relationship to human health.

IMforFUTURE focuses on understanding the biological mechanisms underlying ageing, the biggest single risk factor for most diseases. By providing better high throughput and in depth glycomic and glycoproteomics measurements and better statistical methods for analysis, crucial information towards the understanding of ageing might be become available. IMforFUTURE provides access to unique cohorts for which we develop and apply these new techniques. In addition, we will measure epigenetic data to establish the relationship between glycomics and epigenetics. Glycomic and epigenetic datasets will be integrated with genetic and gene expression datasets which are already available in these cohorts. Analysis of these data will provide new insights and potential biomarkers for accelerated ageing, disease onset and progress.
Research:
All 11 ESRs worked on their individual research projects with a focus on methods for omics data generation (n=4), methods for data analysis (n=4) and data science (n=3). ESRs crossed boundaries and worked jointly to understand the nature of the omics measurements, the assumptions of statistical methods which were used for data analysis, to interpret the results and to discuss their possible impact.

The ESRs developed new techniques for high throughput and in depth glycomic and glycoproteomic data generation. They developed novel network methods for visualisation of the relationships between features of large omic datasets and robust and flexible statistical models for data integration and for assessing the effect of time varying biomarkers on traits. They integrated genetic markers, transcriptomic, epigenetic and glycomic datasets from the consortium cohorts: ORCADES, TwinsUK and Down Syndrome. Application of our novel methods for data generation and analysis resulted in new insights and potential new glycomic biomarkers. Genome wide analysis of genetic and epigenetic markers and their associations with glycans and chronic widespread pain (CWP) resulted in several novel loci. We derived a score based on glycans and clinical variables representing biological age.

Three of the 11 ESRs have already obtained their PhD, and four ESRs have obtained employment (two in industry, one in academia, and one in government).

Training:
Our network comprises ESRs in chemistry, statistics, biology and epidemiology. To train our ESRs we delivered a set of modules which covers the basics of relevant lab techniques, statistical and machine learning techniques, epidemiology and biology. The ESRs also followed a set of modules in commerce and entrepreneurship, complementary skills, and we developed a module for thinking interdisciplinary.

Secondments to partner institutions were key in the development of ESRs’ skills needed to perform high impact research in a multidisciplinary environment and to become scientists able to bridge disciplines.

Finally, organization of the two final workshops, including chairing of sessions, provided the ESRs a fruitful experience. Due to their active role, these activities were lively despite being online and well valued by participants.

Dissemination:
We have already published 35 papers in open access journals (as of September 2021) and there are several submitted papers, including six to a special issue containing contributions of one of the IMforFUTURE workshops. The ESRs have presented their work at international conferences and at our workshops.

Public Engagement:
All ESRs participated in public engagement activities in a primary school in Croatia and at the University of Split. We created a cartoon on the benefits of interdisciplinary collaborations.
We considerably improved methods and workflows for glycan measurements and methods for data analysis. For high throughput measurements we focused on the process underlying established methods to obtain site specific glycosylation. The statistical methods address measurement error, time-varying covariates, heterogeneity and correlation. We identified genetic and epigenetic markers for several glycan traits. We replicated associations between glycans and epigenetic markers, and Down Syndrome. We found novel glycan associations for CWP. Our high throughput method applied to analyse samples from autoimmune hepatitis patients identified a unique glycan profile. A composite biomarker for ageing was developed based on glycans and clinical variables. At the long term, these results will deliver new biomarkers and contribute to personalized medicine, which will improve the quality of life of many patients and reduce costs for the society.

The single most important outcome was the formation of a cohort of multi-disciplinary scientists with unique skills and a toolbox to bring omics research to the next level. They are contributing to and delivering research in academia, industry and governmental institutes.
Cartoon on interdisciplinary research