Advances brought by the BIOMARGIN project

Combining all the skills required to build upon previous findings, BIOMARGIN will offer such opportunities in renal transplantation by integrating several omics approaches (mRNA, miRNA, peptides, proteins, lipids and metabolites) in blood, graft tissue and/or urine (WP3-WP6), in a well-thought out, multistage discovery-to-validation translational programme, following the highest European ethics and regulatory requirements, as well as quality controls and quality assessments at all clinical and analytical steps. It is probably one of the first programmes to pursue such an integrated and systematic research approach.

BIOMARGIN aims to provide validated non-invasive, specific and quantitative biomarkers capable of diagnosing and predicting different forms of renal allograft injury, by:

  • In-biblio and bioinformatics-based refinement of existing candidate biomarkers of renal allograft injury (including verification of their absence in other confounding renal diseases, e.g. for proteomics through the use of the KUPKB website developed and maintained by INSERM)
  • Performing additional, in-depth untargeted analyses to complete these pre-existing biomarkers with lists of candidates, each focussing on the major types of renal graft injuries (T-cell mediated rejection, antibody-mediated rejection, and interstitial fibrosis/tubular atrophy without rejection and without inflammation)
  • Applying stringent Standard Operating Procedures (SOPs)  to all stages of the sample collection, preparation and preservation process, as well as external quality controls or laboratory exchanges of reference samples to check analytical performance.
  • Selecting the most pertinent biomarkers candidates, based on state-of-the art data integration and bioinformatics, with respect to a sound ‘gold standard’, i.e. undisputable phenotypic description of the graft histology by a group of renowned pathologist experts (Dr Laure-Hélène Noël, Paris, external expert; Michael Mihatsch, Basel – external expert; and Jan Ulrich Becher, MHH, Partner 9)
  • Developing transferable, robust, fully validated targeted quantitative techniques, to be used in the last two steps of this programme for the determination of selected biomarker clusters as well as in routine clinics afterwards 
  • Evaluating their diagnostic performance in a large trans-sectional study and their predictive performance in an even larger cohort study, in both adult and paediatric kidney transplant recipients (as it is a unique opportunity to check whether the same biomarkers are also valid in children), where the kinetics of biomarker appearance and disappearance will be characterized.

This will provide clinicians with blood and/or urine diagnostic tests, analytical tools as well as readily available algorithms (through the “BIPART” website) taking into account, in dynamic models, the time evolution of these biomarkers and of other, major risk factors (e.g., donor-specific antibodies, DSA), and help them personalize patient treatment.

As it entails transcriptomics analyses in the graft and a systems biology approach, BIOMARGIN will also help understand the mechanisms involved in the various kidney allograft injury processes. This, combined with mass spectrometry imaging of the graft should offer pathologists new molecular targets for the analysis of renal graft biopsy and may improve, in the process, the “gold standard” diagnosis of graft lesions and injury processes.

Finally, the BIOMARGIN network-Biobank of Urine and Plasma samples (BiBUP) and the BIOmargin BIOmarker DataBase (2BIO-DB) created in the process will offer a unique opportunity for further research on transplantation biomarkers (e.g., proteomics biomarkers in plasma) to members of the Consortium or other researchers.