SCIENTIFIC ACTIVITY (SECOND YEAR)

The aim of the project is the development and application of novel bioinformatic and statistical methods to analyze, using a systems biology approach, different sources of experimental data produced with high-throughput technologie. The applicative focus is the characterization of the role of coding and non-coding RNAs on chronic myeloproliferative neoplasms (MPNs), and in particular in primary myelofibrosis (PMF). Main expected results of the whole project are: i) the discovery and characterization of selected small non-coding RNAs as novel markers associated with the MPNs pathogenesis and prognosis; ii) the reconstruction of regulatory networks in MPN to identify key mixed miRNA-TF circuits deserving functional characterization by targeted experiments. In this report, we present the results of the second year of the project, referring to the original planned tasks. The planned objectives have all been accomplished and further results have been obtained, as detailed in Table 1.
The project is carried out in teamwork. During the second year one formal meeting, for progress report, plus several informal meetings involving subgroups of participants, have been organized. Personnel and travel expenses for participation to scientific meetings related to the project (Table 2), cover the major costs of the second year whereas equipment was mainly acquired in the first year, as appropriate.
New collaborations have been set up and new lines of research opened, thanks also to meetings and seminaries organized in relation to the project topics. For instance, a new collaboration of Dr. S. Bortoluzzi with Dr. Te Kronnie (Univ. of Padova) and Prof. L. Meyer (Ulm University, Germany) started an international research project regarding circular RNAs in hematologic malignancies. Moreover, the group leader submitted several applications for International projects specifically on MPN research, in collaboration with both national enterprises and international research partners, including a SME instrument (Horizon 2020, 2014 call) project and a Qatar National Research Fund project.
The website dedicated to the omics4MPN project (compgen.bio.unipd.it/bioinfo/omics4mpn), created to gather and disseminate main results and products of our scientific activity, including publications, software, facilities, has been updated and filled with new data.

Planned activity of the third year

Currently we are completing with analyses, interpretation and experiments the results of the two lines of research roughly corresponding to WP1 and WP2 and the corresponding manuscripts are in preparation. Other methodological papers are under evaluation or in preparation.
In the next and last year of the project we plan to correlate validated miRNA in PMF granulocytes and their predicted target genes by quantification of their respective levels as a first step.
Then, we will consider both miRNas identified using the RNA-seq-based approach and those outlined by systems biology analyses of expression data. We will start to address the functional relevance of these selected miRNAs by functional tests using clonogenic assays, analysis of differentiation in liquid cultures and of differentiation-associated markers, analysis of cell cycle and apoptosis.
In parallel, we will continue to work on methodological aspects in the field of both data integration, using a systems biology approach, and RNA-seq analysis issues.

Figure 1. Original project timeline with organization in work packages (WP) and tasks, highlighting the activities planned for the second year.

Table 1. Results obtained in the tree planned WPs.

Selected publications

(For an extended list of publications see http://compgen.bio.unipd.it/bioinfo/omics4mpn/dissemination/)