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1.  Integrase-Deficient Lentiviral Vectors Mediate Efficient Gene Transfer to Human Vascular Smooth Muscle Cells with Minimal Genotoxic Risk 
Human Gene Therapy  2012;23(12):1247-1257.
Abstract
We have previously shown that injury-induced neointima formation was rescued by adenoviral-Nogo-B gene delivery. Integrase-competent lentiviral vectors (ICLV) are efficient at gene delivery to vascular cells but present a risk of insertional mutagenesis. Conversely, integrase-deficient lentiviral vectors (IDLV) offer additional benefits through reduced mutagenesis risk, but this has not been evaluated in the context of vascular gene transfer. Here, we have investigated the performance and genetic safety of both counterparts in primary human vascular smooth muscle cells (VSMC) and compared gene transfer efficiency and assessed the genotoxic potential of ICLVs and IDLVs based on their integration frequency and insertional profile in the human genome. Expression of enhanced green fluorescent protein (eGFP) mediated by IDLVs (IDLV-eGFP) demonstrated efficient transgene expression in VSMCs. IDLV gene transfer of Nogo-B mediated efficient overexpression of Nogo-B in VSMCs, leading to phenotypic effects on VSMC migration and proliferation, similar to its ICLV version and unlike its eGFP control and uninfected VSMCs. Large-scale integration site analyses in VSMCs indicated that IDLV-mediated gene transfer gave rise to a very low frequency of genomic integration compared to ICLVs, revealing a close-to-random genomic distribution in VSMCs. This study demonstrates for the first time the potential of IDLVs for safe and efficient vascular gene transfer.
Chick and colleagues demonstrate that integrase-deficient lentiviral (IDLV) vector gene transfer of Nogo-B in human vascular smooth muscle cells (VSMCs) leads to significant phenotypic effects on VSMC migration and proliferation. Large-scale integration analysis in VSMCs revealed that the IDLV vector gave rise to a low frequency of genome integration compared with integrase-competent lentiviral vectors.
doi:10.1089/hum.2012.042
PMCID: PMC3523254  PMID: 22931362
2.  Brain cancer prognosis: independent validation of a clinical bioinformatics approach 
Translational and evidence based medicine can take advantage of biotechnology advances that offer a fast growing variety of high-throughput data for screening molecular activities of genomic, transcriptional, post-transcriptional and translational observations. The clinical information hidden in these data can be clarified with clinical bioinformatics approaches. We have recently proposed a method to analyze different layers of high-throughput (omic) data to preserve the emergent properties that appear in the cellular system when all molecular levels are interacting. We show here that this method applied to brain cancer data can uncover properties (i.e. molecules related to protective versus risky features in different types of brain cancers) that have been independently validated as survival markers, with potential important application in clinical practice.
doi:10.1186/2043-9113-2-2
PMCID: PMC3296594  PMID: 22297051
glioblastoma; survival; system; emergent property; high-throughput biology
3.  Joint analysis of transcriptional and post- transcriptional brain tumor data: searching for emergent properties of cellular systems 
BMC Bioinformatics  2011;12:86.
Background
Advances in biotechnology offer a fast growing variety of high-throughput data for screening molecular activities of genomic, transcriptional, post-transcriptional and translational observations. However, to date, most computational and algorithmic efforts have been directed at mining data from each of these molecular levels (genomic, transcriptional, etc.) separately. In view of the rapid advances in technology (new generation sequencing, high-throughput proteomics) it is important to address the problem of analyzing these data as a whole, i.e. preserving the emergent properties that appear in the cellular system when all molecular levels are interacting. We analyzed one of the (currently) few datasets that provide both transcriptional and post-transcriptional data of the same samples to investigate the possibility to extract more information, using a joint analysis approach.
Results
We use Factor Analysis coupled with pre-established knowledge as a theoretical base to achieve this goal. Our intention is to identify structures that contain information from both mRNAs and miRNAs, and that can explain the complexity of the data. Despite the small sample available, we can show that this approach permits identification of meaningful structures, in particular two polycistronic miRNA genes related to transcriptional activity and likely to be relevant in the discrimination between gliosarcomas and other brain tumors.
Conclusions
This suggests the need to develop methodologies to simultaneously mine information from different levels of biological organization, rather than linking separate analyses performed in parallel.
doi:10.1186/1471-2105-12-86
PMCID: PMC3078861  PMID: 21450054

Results 1-3 (3)