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1.
Nat Commun ; 11(1): 2449, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415096

RESUMO

A comprehensive examination of protein-protein interactions (PPIs) is fundamental for the understanding of cellular machineries. However, limitations in current methodologies often prevent the detection of PPIs with low abundance proteins. To overcome this challenge, we develop a mRNA display with library of even-distribution (md-LED) method that facilitates the detection of low abundance binders with high specificity and sensitivity. As a proof-of-principle, we apply md-LED to IAV NS1 protein. Complementary to AP-MS, md-LED enables us to validate previously described PPIs as well as to identify novel NS1 interactors. We show that interacting with FASN allows NS1 to directly regulate the synthesis of cellular fatty acids. We also use md-LED to identify a mutant of NS1, D92Y, results in a loss of interaction with CPSF1. The use of high-throughput sequencing as the readout for md-LED enables sensitive quantification of interactions, ultimately enabling massively parallel experimentation for the investigation of PPIs.


Assuntos
Biblioteca Gênica , Vírus da Influenza A/metabolismo , Proteínas não Estruturais Virais/metabolismo , Células A549 , Ácido Graxo Sintase Tipo I/metabolismo , Ontologia Genética , Humanos , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/fisiologia , Interferons/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Mutação/genética , Ligação Proteica/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Replicação Viral/efeitos dos fármacos , Replicação Viral/fisiologia
2.
Urol Case Rep ; 9: 51-54, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27713863

RESUMO

Management of men with prostate cancer is fraught with uncertainty as physicians and patients balance efficacy with potential toxicity and diminished quality of life. Utilization of genomics as a prognostic biomarker has improved the informed decision-making process by enabling more rationale treatment choices. Recently investigations have begun to determine whether genomic information from tumor transcriptome data can be used to impact clinical decision-making beyond prognosis. Here we discuss the potential of genomics to alter management of a patient who presented with high-risk prostate adenocarcinoma. We suggest that this information help selecting patients for advanced imaging, chemotherapies, or clinical trial.

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