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To evaluate the specificity of long dsRNAs used in high-throughput RNA interference (RNAi) screens performed at the Drosophila RNAi Screening Center (DRSC), we performed a global analysis of their activity in 30 genome-wide screens completed at our facility. Notably, our analysis predicts that dsRNAs containing > or = 19-nucleotide perfect matches(More)
Receptor tyrosine kinase (RTK) signalling through extracellular-signal-regulated kinases (ERKs) has pivotal roles during metazoan development, underlying processes as diverse as fate determination, differentiation, proliferation, survival, migration and growth. Abnormal RTK/ERK signalling has been extensively documented to contribute to developmental(More)
In contrast to animal-based mutant phenotype assays, recent biochemical and quantitative genetic studies have identified hundreds of potential regulators of known signaling pathways. We discuss the discrepancy between previous models and new data, put forward a different signaling conceptual framework incorporating time-dependent quantitative contributions,(More)
Characterizing the extent and logic of signaling networks is essential to understanding specificity in such physiological and pathophysiological contexts as cell fate decisions and mechanisms of oncogenesis and resistance to chemotherapy. Cell-based RNA interference (RNAi) screens enable the inference of large numbers of genes that regulate signaling(More)
The availability of complete genome sequences from many organisms has yielded the ability to perform high-throughput, genome-wide screens of gene function. Within the past year, rapid advances have been made towards this goal in many major model systems, including yeast, worms, flies, and mammals. Yeast genome-wide screens have taken advantage of libraries(More)
RNA interference (RNAi) and small-molecule approaches are synergistic on multiple levels, from technology and high-throughput screen development to target identification and functional studies. Here, we describe the RNAi screening platform that we have established and made available to the community through the Drosophila RNAi Screening Center at Harvard(More)
Precision medicine is about matching the right drugs to the right patients. Although this approach is technology agnostic, in cancer there is a tendency to make precision medicine synonymous with genomics. However, genome-based cancer therapeutic matching is limited by incomplete biological understanding of the relationship between phenotype and cancer(More)
A label-free quantification strategy including the development of in-house software (NakedQuant) to calculate the average TIC across all spectral counts in tandem affinity purification (TAP)-tagging liquid chromatography-mass spectrometry MS/MS (LC/MS/MS) experiments was applied to a large-scale study of protein complexes in the MAPK portion of the insulin(More)