RNA - Genetherapys
Spoke 7 - Biocomputing

Thanks to a dedicated Information and Communication Technology – ICT infrastructure, Spoke 7 aims to establish a state-of-the-art bioinformatics ecosystem of data and tools, fully integrated with the Italian Node of ELIXIR – the European Research Infrastructure for Life Science Data – that supports the activities of the other horizontal and vertical spokes. The integration of this bioinformatic ecosystem will play a dual role. First, it will provide data-driven findings generating insights and testable hypotheses on novel potential targets (i.e. prediction of neoantigens, splicing isoforms, edited or modified RNAs, 3D structures or interactions, pathways/networks, etc.). Second, it will hold finely tailored RNA-based therapeutics pinpointing optimal solutions to define the integration of experimental assays and biocomputing predictions.

You might be interested in:

Program Who we are Spoke flagships Cross-spoke activities

PROGRAM

The Spoke 7 program will include four parallel Work Packages (WPs).
WP 7.1 will establish a secure IT infrastructure that is GDPR (General Data Protection Regulation) compliant and FAIR (find, access, interoperate, and reuse) data-oriented. WP 7.1.1 will adopt state-of-the-art computing and storage solutions to provide production-ready and interoperable software tools. WP 7.1.2 focuses on the development of a complete bioinformatics framework for the identification of potential RNA therapy targets in different disease models, including those at the single-cell level. Additional activities include the development of a platform for the rational design of gene-targeting RNAs (gRNAs),based on high-throughput CRISPR screens.
WP 7.2 will address the identification of neo-antigens for mRNA vaccinology. Major goals include developing computational workflows that integrate DNA-Seq and RNA-Seq reads from second and third-generation high-throughput platforms for the identification of mutation-, alternative splicing – and RNA editing-driven neo antigens while considering the affinity with HLA class-1 and class-2 types. An additional goal of WP 7.2 is the development of novel methods for profiling transient and non-transient RNA modifications through the analysis of Nanopore-seq data from direct RNA sequencing.

WP 7.3 will focus on the development of several computational approaches. Each approach offers different solutions. One will characterize RNA systems structures, dynamics, and mechanisms through molecular simulations and machine learning approaches. Another will predict the interaction of small molecules/peptides with specific RNAs and identify RNA-based drug candidates. Another approach will unravel the catalytic mechanism of RNA and RNA-based machines through the analysis of their Cryo-EM structures.
WP 7.4 will focus on systems biology and integrative data analysis. WP 7.4 will develop reference models of gene regulatory networks in disease settings and other biological contexts. WP 7.4 will develop AI-based software tools to identify and prioritize targets of RNA drugs and predict their effects. WP 7.4 will develop integrative tools leveraging complex multi-omic datasets to perform patient stratification and identification of disease vulnerabilities. WP 7.4 will also develop predictive approaches to characterize how mutations alter the network of genome-wide regulatory contacts of genes with their enhancers.

Spoke 7 fibreglass

WHO WE ARE

UNIVERSITA DEGLI STUDI DI BARI ALDO MORO
Consiglio Nazionale delle Ricerche
Istituto Italiano di Tecnologia
Università degli Studi di Milano
Università degli Studi di Napoli Federico II Corso Umberto I, 40 80138 Napoli Centralino +39 0812531111 contactcenter@unina.it C.F. 00876220633 PEC ateneo@pec.unina.it
Università degli Studi di Padova
Università degli Studi di Roma “Tor Vergata”

SPOKE FLAGSHIPS

A large biocomputing and storage facility is under construction, which will be equipped with state-of-the-art bioinformatic tools and data resources. In particular, this facility will provide heterogeneous computing resources including a fat server with a large number of Cores and big memory, a server with last-generation GPU cards that can speed up ML/DL/AI algorithms, a fast storage solution based on SSD technologies to reduce the latency of the data. We will also provide a large archive solution for long-term data preservation. All these resources will be available to the end users via both the typical HPC approach, but also using the most cutting-edge cloud technologies.

CROSS-SPOKE ACTIVITIES

Occupying Biocomputing, Spoke 7 serves on-demand requests from other spokes, also through its flagship ICT facility, and with several collaborations that are progressing with other horizontal and vertical spokes.

University of Bari Aldo Moro (UNIBA) collaborates with Spoke 6 in supporting the computational activity for profiling the epitranscriptome by using data from third-generation sequencing technologies (in collaboration with Francesco Nicassio at IIT) and designing guide RNAs for programmable RNA editing (in collaboration with Ernesto Picardi at DBBA-UNIBA and Silvo Conticello at CNR). The optimization and update of existing bioinformatics resources for RNA editing such as the REDIportal database are also carried out in collaboration with Spoke 6.

University of Padua (UNIPD) is establishing important scientific collaborations in the field of molecular dynamics applications in the context of the structural characterization of the RNA structure in solution, and their interaction with therapeutic targets. This is accomplished with the working groups coordinated by Alessandra Magistrato (CNR) and Marco De Vivo (IIT). Furthermore, a collaboration in the development of new molecular docking approaches will be established with Giulio Vistoli (UNIMI). Moreover, the Spoke Leader (UNIBA) coordinates a shared computing infrastructure among participants in the Spoke and its use in specific research areas.

The Department of Pharmacy of University of Naples Federico II (UNINA) is involved in a collaboration with Spoke 6 for the application of computational approaches to characterize RNA systems structures, dynamics, and mechanisms of action and with Spoke 8 for the synthesis of molecular entities to be used in the development of innovative RNA delivery platforms.

The Departments of Computer Science and Biosciences of the University of Milan (UNIMI) will develop all the bioinformatic methods and software tools. Applying and fine-tuning these tools for their application in the context of specific human diseases, the department works in collaboration with the vertical Spokes (Spoke 1-5) and with Spoke 9.

The Department of Pharmaceutical sciences of the University of Milan (UNIMI) is collaborating with Spokes 5 and 8 for the synthesis and the biological evaluation of the designed PNA and morpholino oligonucleotides.