Sviluppo di librerie di anticorpi per l’identificazione di nuovi marcatori diagnostici e terapeutici
Funding programme: FIT Fondo Innovazione Tecnologica, Ministero dello Sviluppo Economico
Start – end year: 2007 – 2009
Partnership
Primm Biotech S.r.l.
Consorzio Milano Ricerche
The project
YOMICS project aimed to the development of a library of antibodies for the identification of new diagnostic and therapeutic biomarkers: specifically, of membrane proteins, acting as signal receptors and transducing signals as growth factors and hormones, that are the targets of pharmacological agents.
Membrane proteins are hard to solubilize and purify because they have both hydrophobic and hydrophilic regions; their structures are therefore difficult to determine experimentally. Computational methods have come to be the first choice for the identification of membrane proteins and for the prediction of their topology. The main aim of this research is to design and implement a computational framework for trans-membrane protein detection.
Earliest computational methods have been Artificial Neural Networks (ANN), due to their capability to capture nonlinear signals: despite their prediction accuracy, ANN are black boxes with no indication of the biological features that the computational model is expected to capture. More recently Hidden Markov Models (HMM) have become the method of choice: the elements of a HMM correspond closely to the biological entities being simulated.
The Yomics™ system is applied for the analysis of the whole human genome, with the objective of identifying 2.000 proteins of interest. The performance of the above system both in terms of flexibility and prediction accuracy makes it a suitable candidate for estimating the number of membrane proteins as well as the frequency of proteins of different topologies to be expected in a given genome.
These libraries used to carry out an innovative analysis of the human proteome in order to identify new diagnostic markers and “targets” therapeutic, through the analysis of collections (Reverse Proteomics).
Implemented in a local version of databases of DNA and protein sequences (EMBL, EntrezGene, Ensembl, VegaGene, UniProt, Pfam) and developed an automated system to update and keep the information synchronized with public resources.
Results indicate that the YOMICS™ antibody library is a tool for systematic protein expression profile analysis that nicely complements the already available commercial antibody collections.
The activity of Consorzio Milano Ricerche focused on the creation of a bioinformatics platform for the selection of genes, consisting in a large amount of data from different sources, both public and private, for extracting useful information. Thus the system LIMS (laboratory information management system) was developed and implemented in order to allow managing the elaborated experimental information.
In close collaboration with Primm, Milano Ricerche developed a gene cloning high throughput system permitting to identify about 2.700 genes, and after experiments and treatments the library contains about 2.500 recombinant clones.
Yomics™ is now a trademarked product of the same Primm S.r.l.