Consiglio Nazionale delle Ricerche

Tipo di prodottoArticolo in rivista
TitoloReconstruction of gene regulatory modules from RNA silencing of IFN-? modulators: experimental set-up and inference method
Anno di pubblicazione2016
FormatoElettronico
Autore/iAngela Grassi 1, Barbara Di Camillo 2, Francesco Ciccarese 3, Valentina Agnusdei 3, Paola Zanovello 1,3, Alberto Amadori 1,3, Lorenzo Finesso 4, Stefano Indraccolo 3, and Gianna Maria Toffolo 2
Affiliazioni autori1 Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy, 2 Department of Information Engineering, University of Padova, Padova, Italy, 3 Istituto Oncologico Veneto - IRCCS, Padova, Italy, 4 Institute of Electronics, Computer and Telecommunication Engineering, CNR, Padova, Italy
Autori CNR e affiliazioni
  • LORENZO FINESSO
Lingua/e
  • inglese
AbstractAbstract Background: Inference of gene regulation from expression data may help to unravel regulatory mechanisms involved in complex diseases or in the action of specific drugs. A challenging task for many researchers working in the field of systems biology is to build up an experiment with a limited budget and produce a dataset suitable to reconstruct putative regulatory modules worth of biological validation. Results: Here, we focus on small-scale gene expression screens and we introduce a novel experimental set-up and a customized method of analysis to make inference on regulatory modules starting from genetic perturbation data, e.g. knockdown and overexpression data. To illustrate the utility of our strategy, it was applied to produce and analyze a dataset of quantitative real-time RT-PCR data, in which interferon-? (IFN-?) transcriptional response in endothelial cells is investigated by RNA silencing of two candidate IFN-? modulators, STAT1 and IFIH1. A putative regulatory module was reconstructed by our method, revealing an intriguing feed-forward loop, in which STAT1 regulates IFIH1 and they both negatively regulate IFNAR1. STAT1 regulation on IFNAR1 was object of experimental validation at the protein level. Conclusions: Detailed description of the experimental set-up and of the analysis procedure is reported, with the intent to be of inspiration for other scientists who want to realize similar experiments to reconstruct gene regulatory modules starting from perturbations of possible regulators. Application of our approach to the study of IFN-? transcriptional response modulators in endothelial cells has led to many interesting novel findings and new biological hypotheses worth of validation.
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Pagine da-
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Pagine totali10
RivistaBMC genomics
Attiva dal 2000
Editore: BioMed Central, - London
Paese di pubblicazione: Regno Unito
Lingua: inglese
ISSN: 1471-2164
Titolo chiave: BMC genomics
Titolo proprio: BMC genomics
Titolo abbreviato: BMC genomics
Titolo alternativo: Genomics
Numero volume della rivista17
Fascicolo della rivista228
DOI10.1186/s12864-016-2525-5
Verificato da refereeSì: Internazionale
Stato della pubblicazionePublished version
Indicizzazione (in banche dati controllate)-
Parole chiaveIFN-? modulators, Gene regulatory modules, RNA silencing, Experimental set-up, Small-scale gene expression screens
Link (URL, URI)http://download.springer.com/static/pdf/194/art%253A10.1186%252Fs12864-016-2525-5.pdf?originUrl=http%3A%2F%2Fbmcgenomics.biomedcentral.com%2Farticle%2F10.1186%2Fs12864-016-2525-5&token2=exp=1457950467~acl=%2Fstatic%2Fpdf%2F194%2Fart%25253A10.1186%25252Fs12864-016-2525-5.pdf*~hmac=f9552d3aa1e2629a6d4cc5650368181cbdce410e41c9c223a77c3c28fb5e1a85
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Strutture CNR
  • IEIIT — Istituto di elettronica e di ingegneria dell'informazione e delle telecomunicazioni
Moduli CNR
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    BMC-2016-paper (documento privato )
    Tipo documento: application/pdf