Poster Session 3.H - Pharmaceutical Sciences and Health Technologies
Váczy-Földi, Máté, MSc
XA6S0Q
Department of Pharmacology and Pharmacotherapy, Semmelweis University
+36 20 504 7462
vaczy.foldi.mate@semmelweis.hu
miRNAtarget: a Network-based Solution and Benchmarking Framework for Predicting Transcriptome-wide Concerted Regulatory Effects of microRNAs
Máté Váczy-Földi1,2,3, Bettina Benczik1,2,3, Zsolt Papp1,2, Olivér Balogh1,2, Barnabás Váradi1,2, Dóra Bihary1,2, Zoltán Bereczki1,2, András Makkos1,2,3, Anikó Görbe1,2,3,4, Péter Bencsik3,4, Péter Ferdinandy1,2,3, Bence Ágg1,2,3
1: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Hungary
2: Center for Pharmacology and Drug Research & Development, Semmelweis University, Hungary
3: Pharmahungary Group, Hungary
4: Department of Pharmacology and Pharmacotherapy, University of Szeged, Hungary
Poszter
Poster Session 3.H - Pharmaceutical Sciences and Health Technologies
English
Pharmaceutical Sciences and Health Technologies
Introduction
The development of small RNA therapeutics has grown explosively over the past decade, which necessitates the accurate prediction of their effects to ensure therapeutic efficacy and avoid off-target toxicity. This prediction task poses an even greater challenge for the combinatorial effects of multiple microRNAs.
Aims
To address this problem, we aimed to create a robust evaluation framework and a comprehensive benchmarking dataset for prediction tools, and to demonstrate their applicability through a comparative performance analysis of our network topology-based model, miRNAtarget™.
Methods
A ground truth benchmark dataset of differential gene expression profiles was constructed by applying a uniform bioinformatics pipeline to paired small RNA- and bulk mRNA-sequencing data from five human and mouse studies in the Gene Expression Omnibus (GEO). This dataset was then utilized within a rigorous validation framework to perform a comparative performance analysis. The predictive accuracy of the complete, multi-source miRNAtarget™ model was evaluated against its own single-source variants, which rely exclusively on individual databases (TargetScan, miRDB, miRTarBase), and a random classifier.
Result
Our analysis revealed that predictive performance of miRNAtarget is dependent on the evaluation metric. When evaluating by the magnitude of predicted effect (top ten percent by absolute value of change), the single-source miRNAtarget variant relying on miRDB was the top performer (6/17 comparisons). However, when evaluating by directional accuracy (top ten percent of most up- and downregulated predictions), the TargetScan-based variant was better (8/17 comparisons).
Conclusion
We have defined the task of predicting the combinatorial transcriptomic effects of microRNAs and provided the first unified framework and public dataset to address it. This work establishes a necessary benchmark for the rigorous and reproducible comparison of future prediction algorithms.
Funding
Project no. RRF-2.3.1-21-2022-00003 has been implemented with the support provided by the European Union. Supported by the 2024-2.1.2-EKÖP-KDP New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund. This study has been supported by a Semmelweis 250+ Excellence Fellowship.
Semmelweis University
Dr. Bence Ágg, MD PhD
I do not give consent to the publication of my abstract on the website of the congress.
in doctoral studies before complex exam (PhD)
Szabad
elfogadva
poszter
nem rendelkezett róla
9071
13:42
13:45