The rules of miRNA-target interactions

Descrizione del progetto

Individuare i bersagli dei microRNA

I microRNA (miRNA) sono piccole molecole di RNA che svolgono un ruolo fondamentale nella regolazione dell’espressione genica. Prove sempre più numerose indicano la loro importanza in contesti sia fisiologici che patologici, rendendoli uno dei principali obiettivi della ricerca biomedica; ciononostante, la previsione dei bersagli genici precisi dei miRNA costituisce tuttora un’importante sfida computazionale. Il progetto miRules, finanziato dall’UE, svilupperà una strategia bioinformatica avanzata al fine di comprendere il meccanismo con cui i miRNA trovano i loro bersagli. I ricercatori si baseranno sullo strumento di apprendimento profondo miRBind e integreranno nuove metodologie per migliorare l’accuratezza della previsione dei bersagli dei miRNA, gettando nel complesso le basi per lo sviluppo di strumenti avanzati di apprendimento automatico che supporteranno la ricerca di base e traslazionale nel campo della biologia dell’RNA.

Obiettivo

Micro RNAs (miRNAs) are short regulatory RNA molecules which modulate the levels of RNA and proteins in cells.
Understanding the role of miRNAs in health and disease is a field with high engagement in molecular biology and biomedicine, with over 50 000 scientific articles published in the past 5 years (PubMed search “microrna[MeSH Terms]”).
However, predicting their molecular targets is still a major unsolved challenge, and the state-of-the-art bioinformatic solutions for this task remain far from perfect.
First, the task requires an exceptionally high accuracy and precision, as it can be compared to looking for a few hundred needles in a haystack: a few hundred targets among hundreds of thousands of transcripts. Second, the true mechanism of target binding is still unknown, which necessitates the use of heuristic approaches - ones that seem to work often enough, but are not necessarily related to the way miRNAs actually find their targets.

The aim of this project is to use bioinformatic methods to gain more knowledge about the mechanisms of miRNA-target interactions. We will approach this problem from several angles: 1) Using the deep learning methodology recently developed by the host group (miRBind), which reaches a single nucleotide resolution in its predictions; 2) Analyzing the interactions from an evolutionary perspective; 3) Developing a customized pairwise alignment algorithm combined with a dedicated statistical methodology. The Researcher will benefit from this project by gaining experience in the field of genomics in a multidisciplinary, collaborative environment.

In the future, the results of this project will enable creating knowledge-driven machine learning models for improved prediction of the molecular targets of miRNAs, which will facilitate the fundamental and applied research on the complex biology of these molecules.