An understanding towards genetics and epigenetics is essential to cope up with the paradigm shift which is underway. Personalized medicine and gene therapy will confluence the days to come.
This review highlights traditional approaches as well as current advancements in the analysis of the gene expression data from cancer perspective.
Due to improvements in biometric instrumentation and automation, it has become easier to collect a lot of experimental data in molecular biology.
Analysis of such data is extremely important as it leads to knowledge discovery that can be validated by experiments. Previously, the diagnosis of complex genetic diseases has conventionally been done based on the non-molecular characteristics like kind of tumor tissue, pathological characteristics, and clinical phase.
The microarray data can be well accounted for high dimensional space and noise. Same were the reasons for ineffective and imprecise results. Several machine learning and data mining techniques are presently applied for identifying cancer using gene expression data.
While differences in efficiency do exist, none of the well-established approaches is uniformly superior to others. The quality of algorithm is important, but is not in itself a guarantee of the quality of a specific data analysis.
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Assessing the clinical utility of cancer genomic and proteomic data across tu...Gul Muneer
Molecular profiling of tumors promises to advance the clinical
management of cancer, but the benefits of integrating
molecular data with traditional clinical variables have not been
systematically studied. Here we retrospectively predict patient
survival using diverse molecular data (somatic copy-number
alteration, DNA methylation and mRNA, microRNA and protein
expression) from 953 samples of four cancer types from The
Cancer Genome Atlas project. We find that incorporating
molecular data with clinical variables yields statistically
significantly improved predictions (FDR < 0.05) for three
cancers but those quantitative gains were limited (2.2–23.9%).
Additional analyses revealed little predictive power across
tumor types except for one case. In clinically relevant genes,
we identified 10,281 somatic alterations across 12 cancer types
in 2,928 of 3,277 patients (89.4%), many of which would
not be revealed in single-tumor analyses. Our study provides
a starting point and resources, including an open-access
model evaluation platform, for building reliable prognostic and
therapeutic strategies that incorporate molecular data
An understanding towards genetics and epigenetics is essential to cope up with the paradigm shift which is underway. Personalized medicine and gene therapy will confluence the days to come.
This review highlights traditional approaches as well as current advancements in the analysis of the gene expression data from cancer perspective.
Due to improvements in biometric instrumentation and automation, it has become easier to collect a lot of experimental data in molecular biology.
Analysis of such data is extremely important as it leads to knowledge discovery that can be validated by experiments. Previously, the diagnosis of complex genetic diseases has conventionally been done based on the non-molecular characteristics like kind of tumor tissue, pathological characteristics, and clinical phase.
The microarray data can be well accounted for high dimensional space and noise. Same were the reasons for ineffective and imprecise results. Several machine learning and data mining techniques are presently applied for identifying cancer using gene expression data.
While differences in efficiency do exist, none of the well-established approaches is uniformly superior to others. The quality of algorithm is important, but is not in itself a guarantee of the quality of a specific data analysis.
http://kaashivinfotech.com/
http://inplanttrainingchennai.com/
http://inplanttraining-in-chennai.com/
http://internshipinchennai.in/
http://inplant-training.org/
http://kernelmind.com/
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Assessing the clinical utility of cancer genomic and proteomic data across tu...Gul Muneer
Molecular profiling of tumors promises to advance the clinical
management of cancer, but the benefits of integrating
molecular data with traditional clinical variables have not been
systematically studied. Here we retrospectively predict patient
survival using diverse molecular data (somatic copy-number
alteration, DNA methylation and mRNA, microRNA and protein
expression) from 953 samples of four cancer types from The
Cancer Genome Atlas project. We find that incorporating
molecular data with clinical variables yields statistically
significantly improved predictions (FDR < 0.05) for three
cancers but those quantitative gains were limited (2.2–23.9%).
Additional analyses revealed little predictive power across
tumor types except for one case. In clinically relevant genes,
we identified 10,281 somatic alterations across 12 cancer types
in 2,928 of 3,277 patients (89.4%), many of which would
not be revealed in single-tumor analyses. Our study provides
a starting point and resources, including an open-access
model evaluation platform, for building reliable prognostic and
therapeutic strategies that incorporate molecular data
Proteogenomic analysis of human colon cancer reveals new therapeutic opportun...Gul Muneer
We performed the first proteogenomic study on a prospectively collected colon cancer cohort. Comparative proteomic and phosphoproteomic analysis of paired tumor and normal adjacent tissues produced a catalog of colon cancer-associated proteins and phosphosites, including known and putative new biomarkers, drug targets, and cancer/testis antigens. Proteogenomic integration not only prioritized genomically inferred targets, such as copy-number drivers and mutation-derived neoantigens, but also yielded novel findings. Phosphoproteomics data associated Rb phosphorylation with increased proliferation and decreased apoptosis in colon cancer, which explains why this classical tumor suppressor is amplified in colon tumors and suggests a rationale for targeting Rb phosphorylation in colon cancer. Proteomics identified an association between decreased CD8 T cell infiltration and increased glycolysis in microsatellite instability-high (MSI-H) tumors, suggesting glycolysis as a potential target to overcome the resistance of MSI-H tumors to immune checkpoint blockade. Proteogenomics presents new avenues for biological discoveries and therapeutic development.
Final presentation for BIOL405, NSC, Spring 2014. Presented by Kevin Hugins and Duy-Khiem Chanh Pham. This presentation addressed the use of Chimeric Antigen Receptors for gene therapy for cancer. Gene therapy was first conceptualized to alter debilitating fates of genetic diseases. Gene therapy technology can help introduce new functional DNA to replace mutated genes. The idea first arose in 1972 when Friedmann and Roblin authored a paper, “Gene therapy for human genetic disease?”, demonstrating that exogenous DNA can be taken up by mammalian cells (1). They proposed that the same procedure could be done on humans to correct genetic defects by introducing therapeutic DNA. Currently, genetic modification of T lymphocytes has been the major area of research for treating malignant tumors. This technique seeks to create chimeric antigen receptor (CAR) in T cells by genetically modifying them in vitro and reintroduce them back into blood circulation. The T cells are unique to every patient and the chimeric antigen receptors are unique to the tumor that it is targeting.
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neu...Gul Muneer
Systemic cross-talk between lung tumors and bones
Bone marrow–derived myeloid cells can accumulate within tumors and foster
cancer outgrowth. Local immune-neoplastic interactions have been intensively
investigated, but the contribution of the systemic host environment to tumor growth
remains poorly understood. Here, we show in mice and cancer patients (n = 70) that
lung adenocarcinomas increase bone stromal activity in the absence of bone
metastasis. Animal studies reveal that the cancer-induced bone phenotype involves
bone-resident osteocalcin-expressing (Ocn+) osteoblastic cells. These cells promote
cancer by remotely supplying a distinct subset of tumor-infiltrating SiglecFhigh
neutrophils, which exhibit cancer-promoting properties. Experimentally reducing
Ocn+ cell numbers suppresses the neutrophil response and lung tumor outgrowth.
These observations posit osteoblasts as remote regulators of lung cancer and
identify SiglecFhigh neutrophils as myeloid cell effectors of the osteoblast-driven
protumoral response
Lynette M. Sholl, MD, and Geoffrey R. Oxnard, MD, prepared useful practice aids pertaining to EGFR mutation-positive lung cancer in this CME/MOC activity titled "Molecular Testing for EGFR Mutations in the Context of a Changing Treatment Landscape, Evolving Testing Options, and Updated Guidelines: What Pathologists Need to Know and Do." For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2sPyPNn. CME/MOC credit will be available until February 5, 2020.
Invicta eshre-poster-pregnancy rate after frozen blastocystINVICTA GENETICS
Assessment of pregnancy rate after comprehensive chromosome screening using next-generation sequencing-based preimplantation genetic diagnosis (NGS PGD) of trophectoderm in frozen blastocyst transfer.
E1512 Trial Spotlight for May 2013 ECOG-ACRIN NewsletterSara Bucknam
E1512 Trial spotlight for ECOG-ACRIN Newsletter. E1512 is a randomized, three‐arm phase II trial investigating the clinical efficacy and safety of erlotinib alone, cabozantinib alone, or erlotinib plus cabozantinib as second‐ or third‐line therapy in patients with EGFR wild‐type NSCLC.
Conference on Receptor Tyrosine kinase quantiftation by Ms2plex by X. Morge -...Florence Fombertasse
This tools are usefull for a better comprehension of the cancer physiopathology in order for example to qualify the cell lines but also to enable to define a therapeutical protocol.
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Proteogenomic analysis of human colon cancer reveals new therapeutic opportun...Gul Muneer
We performed the first proteogenomic study on a prospectively collected colon cancer cohort. Comparative proteomic and phosphoproteomic analysis of paired tumor and normal adjacent tissues produced a catalog of colon cancer-associated proteins and phosphosites, including known and putative new biomarkers, drug targets, and cancer/testis antigens. Proteogenomic integration not only prioritized genomically inferred targets, such as copy-number drivers and mutation-derived neoantigens, but also yielded novel findings. Phosphoproteomics data associated Rb phosphorylation with increased proliferation and decreased apoptosis in colon cancer, which explains why this classical tumor suppressor is amplified in colon tumors and suggests a rationale for targeting Rb phosphorylation in colon cancer. Proteomics identified an association between decreased CD8 T cell infiltration and increased glycolysis in microsatellite instability-high (MSI-H) tumors, suggesting glycolysis as a potential target to overcome the resistance of MSI-H tumors to immune checkpoint blockade. Proteogenomics presents new avenues for biological discoveries and therapeutic development.
Final presentation for BIOL405, NSC, Spring 2014. Presented by Kevin Hugins and Duy-Khiem Chanh Pham. This presentation addressed the use of Chimeric Antigen Receptors for gene therapy for cancer. Gene therapy was first conceptualized to alter debilitating fates of genetic diseases. Gene therapy technology can help introduce new functional DNA to replace mutated genes. The idea first arose in 1972 when Friedmann and Roblin authored a paper, “Gene therapy for human genetic disease?”, demonstrating that exogenous DNA can be taken up by mammalian cells (1). They proposed that the same procedure could be done on humans to correct genetic defects by introducing therapeutic DNA. Currently, genetic modification of T lymphocytes has been the major area of research for treating malignant tumors. This technique seeks to create chimeric antigen receptor (CAR) in T cells by genetically modifying them in vitro and reintroduce them back into blood circulation. The T cells are unique to every patient and the chimeric antigen receptors are unique to the tumor that it is targeting.
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neu...Gul Muneer
Systemic cross-talk between lung tumors and bones
Bone marrow–derived myeloid cells can accumulate within tumors and foster
cancer outgrowth. Local immune-neoplastic interactions have been intensively
investigated, but the contribution of the systemic host environment to tumor growth
remains poorly understood. Here, we show in mice and cancer patients (n = 70) that
lung adenocarcinomas increase bone stromal activity in the absence of bone
metastasis. Animal studies reveal that the cancer-induced bone phenotype involves
bone-resident osteocalcin-expressing (Ocn+) osteoblastic cells. These cells promote
cancer by remotely supplying a distinct subset of tumor-infiltrating SiglecFhigh
neutrophils, which exhibit cancer-promoting properties. Experimentally reducing
Ocn+ cell numbers suppresses the neutrophil response and lung tumor outgrowth.
These observations posit osteoblasts as remote regulators of lung cancer and
identify SiglecFhigh neutrophils as myeloid cell effectors of the osteoblast-driven
protumoral response
Lynette M. Sholl, MD, and Geoffrey R. Oxnard, MD, prepared useful practice aids pertaining to EGFR mutation-positive lung cancer in this CME/MOC activity titled "Molecular Testing for EGFR Mutations in the Context of a Changing Treatment Landscape, Evolving Testing Options, and Updated Guidelines: What Pathologists Need to Know and Do." For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2sPyPNn. CME/MOC credit will be available until February 5, 2020.
Invicta eshre-poster-pregnancy rate after frozen blastocystINVICTA GENETICS
Assessment of pregnancy rate after comprehensive chromosome screening using next-generation sequencing-based preimplantation genetic diagnosis (NGS PGD) of trophectoderm in frozen blastocyst transfer.
E1512 Trial Spotlight for May 2013 ECOG-ACRIN NewsletterSara Bucknam
E1512 Trial spotlight for ECOG-ACRIN Newsletter. E1512 is a randomized, three‐arm phase II trial investigating the clinical efficacy and safety of erlotinib alone, cabozantinib alone, or erlotinib plus cabozantinib as second‐ or third‐line therapy in patients with EGFR wild‐type NSCLC.
Conference on Receptor Tyrosine kinase quantiftation by Ms2plex by X. Morge -...Florence Fombertasse
This tools are usefull for a better comprehension of the cancer physiopathology in order for example to qualify the cell lines but also to enable to define a therapeutical protocol.
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The Live Seminar examined the legal instruments and policy tools available to protect the environment in situations of armed conflict. Against the backdrop of the release of a United Nations Environment Programme report, this Seminar addressed the following questions:
* How are notions such as “widespread,” “long-term,” and “severe” damage to the environment defined in international humanitarian law and international criminal law?
* Which mechanisms could best monitor legal infringements pertaining to, and address claims for, environmental damage sustained during armed conflict?
* In what ways, if any, do international and domestic environmental law interact with international humanitarian law during armed conflict?
These questions were examined by looking at the level and types of legal protection afforded to the environment in both international and non-international armed conflicts.
Naz Modirzadeh (Associate Director at the Program on Humanitarian Policy and Conflict Research) hosted the discussion.
Panelists included:
Dr. Karen Hulme, University of Essex, School of Law
Professor Eric Jensen, Fordham University School of Law
Tara Smith, Irish Center for Human Rights
A short presentation on presenting data - a follow up to presentation thoughts. A lot of the content was based on the excellent slideology book by Duarte Design
World: Millet - Market Report. Analysis And Forecast To 2020IndexBox Marketing
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Green Organics India, Royal Nut Company, Sustainable Seed Co., Reliant Int, Anita's Organic
Purpose: An inherited mutation in KRAS (LCS6-variant or rs61764370) results in altered control of the KRAS oncogene. We studied this biomarker’s correlation to anti-EGFR monoclonal antibody (mAb) therapy
response in patients with metastatic colorectal cancer.
Experimental Design: LCS6-variant and KRAS/BRAF mutational status was determined in 512 patients
with metastatic colorectal cancer treated with salvage anti-EGFR mAb therapy, and findings correlated with
outcome. Reporters were tested in colon cancer cell lines to evaluate the differential response of the LCS6-
variant allele to therapy exposure.
Results: In this study, 21.2% (109 of 512) of patients with metastatic colorectal cancer had the LCS6-
variant (TG/GG), which was found twice as frequently in the BRAF-mutated versus the wild-type (WT) group
(P = 0.03). LCS6-variant patients had significantly longer progression- free survival (PFS) with anti-EGFR
mAb monotherapy treatment in the whole cohort (16.85 vs. 7.85 weeks; P = 0.019) and in the double WT
(KRAS and BRAF) patient population (18 vs. 10.4 weeks; P = 0.039). Combination therapy (mAbs plus
chemotherapy) led to improved PFS and overall survival (OS) for nonvariant patients, and brought their
outcome to levels comparable with LCS6-variant patients receiving anti-EGFR mAb monotherapy. Combination
therapy did not lead to improved PFS or OS for LCS6-variant patients. Cell line studies confirmed a
unique response of the LCS6-variant allele to both anti-EGFR mAb monotherapy and chemotherapy.
Conclusions: LCS6-variant patients with metastatic colorectal cancer have an excellent response to anti-EGFR
mAb monotherapy, without any benefit from the addition of chemotherapy. These findings further confirm
the importance of thismutation as a biomarker of anti-EGFR mAb response in patients with metastatic colorectal cancer, and warrant further prospective confirmation.
Epstein-Barr virus genetic variants are associated with multiple sclerosis.Mutiple Sclerosis
Rosella Mechelli, Caterina Manzari, Claudia Policano, Anita Annese, Ernesto Picardi, Renato Umeton, Arianna Fornasiero, Anna Maria D’Erchia, Maria Chiara Buscarinu, Cristina Agliardi, Viviana Annibali, Barbara Serafini, Barbara Rosicarelli, Silvia Romano, Daniela F. Angelini, Vito A.G. Ricigliano, Fabio Buttari, Luca Battistini, Diego Centonze, Franca R. Guerini, Sandra D’Alfonso, Graziano Pesole, Marco Salvetti, Giovanni Ristori
OBJECTIVE:
We analyzed the Epstein-Barr nuclear antigen 2 (EBNA2) gene, which contains the most variable region of the viral genome, in persons with multiple sclerosis (MS) and control subjects to verify whether virus genetic variants are involved in disease development.
METHODS:
A seminested PCR approach and Sanger sequencing were used to analyze EBNA2 in 53 patients and 38 matched healthy donors (HDs). High-throughput sequencing by Illumina MiSeq was also applied in a subgroup of donors (17 patients and 17 HDs). Patients underwent gadolinium-enhanced MRI and human leucocyte antigen typing.
RESULTS:
MS risk significantly correlated with an excess of 1.2 allele (odds ratio [OR] = 5.13; 95% confidence interval [CI] 1.84-14.32; p = 0.016) and underrepresentation of 1.3B allele (OR = 0.23; 95% CI 0.08-0.51; p = 0.0006). We identified new genetic variants, mostly 1.2 allele- and MS-associated (especially amino acid variation at position 245; OR = 9.4; 95% CI 1.19-78.72; p = 0.0123). In all cases, the consensus sequence from deep sequencing confirmed Sanger sequencing (including the cosegregation of newly identified variants with known EBNA2 alleles) and showed that the extent of genotype intraindividual variability was higher than expected: rare EBNA2 variants were detected in all HDs and patients with MS (range 1-17 and 3-19, respectively). EBNA2 variants did not seem to correlate with human leucocyte antigen typing or clinical/MRI features.
CONCLUSIONS:
Our study unveils a strong association between Epstein-Barr virus genomic variants and MS, reinforcing the idea that Epstein-Barr virus contributes to disease development.
A KRAS-variant is a Biomarker of Poor Outcome, Platinum Chemotherapy Resistan...UCLA
Germ-line variants in the 3′ untranslated region (3′UTR) of cancer genes disrupting microRNA (miRNA) regulation have recently been associated with cancer risk. A variant in the 3′UTR of the KRAS oncogene, referred to as the KRAS-variant, is associated with both cancer risk and altered tumor biology. Here we test the hypothesis that the KRAS-variant can act as a biomarker of outcome in epithelial ovarian cancer (EOC), and investigate the cause of altered outcome in KRAS-variant positive EOC patients. As this variant appears to be associated with tumor biology, we additionally test the hypothesis that this variant can be directly targeted to impact cell survival.
EOC patients with complete clinical data were genotyped for the KRAS-variant and analyzed for outcome (n=536), response to neoadjuvant chemotherapy (n=125), and platinum resistance (n=306). Outcome was separately analyzed for women with known BRCA mutations (n=79). Gene expression was analyzed on a subset of tumors with available tissue. Cell lines were employed to confirm altered sensitivity to chemotherapy with the KRAS-variant. The KRAS- variant was directly targeted through siRNA/miRNA oligonucleotides in cell lines and survival was measured.
Post-menopausal EOC patients with the KRAS-variant were significantly more likely to die of ovarian cancer by multivariate analysis (HR=1.67, 95% CI=1.09–2.57, p=0.019, n=279). Possibly explaining this finding, EOC patients with the KRAS-variant were significantly more likely to be platinum resistant (OR=3.18, CI=1.31–7.72, p=0.0106, n=291). Additionally, direct targeting of the KRAS-variant led to a significant reduction in EOC cell growth and survival in vitro.
These findings confirm the importance of the KRAS-variant in EOC, and indicate that the KRAS- variant is a biomarker of poor outcome in EOC likely due to platinum resistance. In addition, this work supports the hypothesis that these tumors have continued dependence on such 3′UTR lesions, and that direct targeting may be a viable future treatment approach.
A 3′-untranslated region KRAS variant and triple-negative breast cancer: a ca...UCLA
The KRAS-variant might be a genetic marker for development of triple negative breast cancer in premenopausal women, and altered gene and miRNA expression signatures should enable molecular and biological stratification of patients with this subgroup of
breast cancer.
Diagonsis of cancer through saliva.pptxZaidAhmad42
Human saliva is an ideal body fluid for developing non-invasive diagnostics. Saliva contains naturally-occurring nanoparticles with unique structural and biochemical characteristics.
Open Source Pharma /Genomics and clinical practice / Prof Hosur opensourcepharmafound
Access to Research
Date 11-08-2018
Venue Conference HAll NIAS IISc campus
Conference and workshops for clinical practitioners to introduce them to modern tools and an alternative approach to modern scientific research.
Purpose
1. Build a network of physicians across the country
2 Train physicians to analyse clinical data and restructure it to make it compatible with research standards
3. Introduce modern tools to understand the mechanism of actions of medicine
4. Introduce artificial intelligence and machine learning to clinical practitioners to support decision-making processes
Access to Science
Clinical experience and traditional knowledge are important sources of data that affect decision making processes in modern healthcare systems. This data should be made accessible for scientific evaluation and validation to improve healthcare worldwide. The Open Source Pharma Foundation believes that clinical practitioners from various disciplines should have the right to access research so that they can help identify problems, contribute their scientific knowledge, and support the discovery ecosystem.
Background
The majority of medical practitioners working on the ground level with patients do not take part in open clinical research worldwide. However, the data collected and owned by them plays an important role in establishing better discovery pathways. Through this workshop, we seek to open opportunities to enhance health care systems around the world and to overcome the following challenges faced by medical practitioners.
1. Regulatory limitations
2. Academic limitations
3. Time constraints
4. Lack of access to modern tools
5. Lack of access to research facilities
1. Translational Medicine @ UniSa - ISSN 2239-9747 2014, Special Issue (1): 56
Giornate della Facoltà di Farmacia e Medicina a Salerno
Campus di Fisciano dell'Università di Salerno presso il Dipartimento di Farmacia
22 e 23 maggio 2014
56
Università degli Studi di Salerno
Analysis by RNA-Seq of Ligand-Actived Estrogen Receptor Beta (ERβ) Effects
on Alternative Splicing Patterns in Breast Cancer Cells
Santamaria G1, Rinaldi A1, Dago DN1,2, Giurato G1, Ravo M1, Ricciardi L1, Cordella A1,3, Weisz A1
1Department of Medicine and Surgery, Laboratory of Molecular Medicine and Genomics, University of
Salerno, Baronissi (SA), Italy;
2 UFR Sciences Biologiques, Université Peleforo Gon Coulibaly, Korhogo, Costa d'Avorio;
3Fondazione IRCCS SDN, Napoli (NA), Italy.
RNA-Seq is a powerful technology for gene expression profiling. In addition, the sequence read
length and coverage allowed by current sequencing technologies allows also an accurate estimation
of RNA isoforms generated by alternative splicing (AS).
AS contributes to the complexity of higher eukaryotes and its disruption is a major source of human
disease. AS is the process in which a pre-mRNA transcripts can be spliced in different ways to
obtain various new mRNAs. Spliceosome activity has been shown to depend upon a large number
of components, including hnRNPs (heterogeneous nuclear ribonucleoproteins), SR proteins
(serine/arginine-rich proteins) and U1, U2, U3 and U4 spliceosomal small nuclear
ribonucleoproteins. Recent studies have demonstrated that significant changes in AS events are
related to breast cancer (BC), suggesting that an understanding of these events could increase
prognosis accuracy and open new frontiers for research in molecular oncology.
Previous genomics and proteomics studies revealed that the different biological activity of estrogen
receptor (ER) β respect to α relies also on components of the splicing machinery, confirming the
relationship between ERβ and mRNA splicing.
To examine these events in a controlled environment, we investigated splicing events specifically
affected by ERβ in hormone-responsive breast cancer cells to search for novel insights on the
effects of this receptor on the biological and clinical phenotype of tumors. Results show that a
significant number of splicing events are either induced or prevented by ERβ in these cells,
indicating an impact of this ER subtype on post-transcriptional gene regulation via AS in hormone-
responsive BC.
RESEARCH SUPPORTED BY: AIRC (Grant IG-13176), MIUR (PRIN 2010LC747T_002), EU
COST (Action BM1006 ‘SeqAhead’), CNR InterOmics Flagship Project and a ‘Vladimir
Ashkenazy’ AIRC fellowship (to M. Ravo).