Akademik Veri Yönetim Sistemi
Akyerli Boylu C., Özduman K., Bilgüvar K., Yakıcıer M. C., Erşen Danyeli A. (Yürütücü)
TÜBİTAK Uluslararası Çoklu İşbirliği Projesi , 2025 - 2028
Understanding the epigenetics of brain tumors is vital, as it allows distinguishing tumors with
unprecedented precision, guiding precise classification and tailored therapeutic approaches.
Consequently, methylation has even been incorporated as a diagnostic criterion in the WHO
Classification of Brain Tumors 2021. A paramount tool when using DNA methylation for
classification ? especially for brain tumors is the Heidelberg classifier, developed by the
research group coordinating DC2M-TAEC(available on www.molecularneuropathology.org)
This computer algorithm assigns any given specimen to the correct diagnosis based on its
methylation data. However, using this algorithm currently requires data input that is
generated in a tedious, lengthy and costly manner. This limits its global implementation due
to unavailability of resources and the timeconsuming nature of the protocol, which ultimately
hampers patient care. With DC2M-TAEC, we will leverage a rapid and more accessible
platform to simultaneously generate methylation and sequencing results: long-read, or so
called nanopore sequencing; a PCR-free, single-molecule sequencing approach. We will
paradigmatically establish this method in a large center in which molecular profiling is so far
not regularly available due to the aforementioned hurdles. Within this consortium, experts
from Heidelberg, Oslo, Istanbul, and Toronto join forces. The Heidelberg group will focus on
the bioinformatics behind methylation-based classification
and adapting their algorithm to accept various data types as input ? including nanopore
data. This classification tool will then be optimized and tested for analysis of single-cell DNA
nanopore data, to examine epigenetic changes in the tumor and its microenvironment over
time. The sample processing and sequencing will be optimized for intra-operative
classification in Oslo, which will then be implemented with the adapted Heidelberg classifier
in Istanbul. Lastly, to complete the full circle of diagnostic potential, Nanopore sequencing
will be devised for analyzing liquid biopsy samples in Toronto, e.g. for pre-operative usage
or disease monitoring. Ultimately, the resulting diagnostic workflow, demonstrated to be
globally feasible, will allow individualized and risk-adapted care for patients with brain
tumors. This tremendous translational impact is emphasized by the fact that the approaches
will span early detection, surgery planning, intra-operative surgery guidance, treatment
monitoring, and biological insight by detection of resistance mechanisms. This project can
serve as a proof of concept to further establish nanopore sequencing beyond the field of
neuro-oncology in the future.