Deciphering cis-regulatory logic with 100 million synthetic promoters (MNase)
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PROVIDER: PRJNA414115 | ENA |
REPOSITORIES: ENA
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Project description:Deciphering cis-regulatory logic with 100 million synthetic promoters
| PRJNA414104 | ENA
Project description:In order to generate data suitable to decipher cis-regulatory logic, we generated ~100 million synthetic promoters (in yeast) comprised of random DNA and measured their expression by FACS (sorting into 18 bins).
2019-01-01 | GSE104878 | GEO
Project description:In order to test our model of gene regulation, we measured nucleosome occupancy of our random promoter library using Mnase-seq.
2019-01-01 | GSE104903 | GEO
Project description: Not available
| S-EPMC6954276 | biostudies-literature
Project description:Machine learning methods, particularly neural networks trained on large datasets, are transforming how scientists approach scientific discovery and experimental design. However, current state-of-the-art neural networks are limited by their uninterpretability: despite providing accurate predictions, they cannot describe how they arrived at their predictions. Here, using an ``interpretable-by-design'' approach, we present a neural network model that provides insights into RNA splicing, a fundamental process in the transfer of genomic information into functional biochemical products. Although we designed our model to emphasize interpretability, its predictive accuracy is on par with state-of-the-art models. To demonstrate the model's interpretability, we introduce a visualization that, for any given exon, allows us to trace and quantify the entire decision process from input sequence to output splicing prediction. Importantly, the model revealed novel components of the splicing logic, which we experimentally validated. This study highlights how interpretable machine learning can advance scientific discovery.
2022-10-01 | GSE200096 | GEO
Project description: Not available
| S-EPMC6475595 | biostudies-literature
Project description:Pulsed SILAC approaches allow measurement of protein dynamics, including protein translation and degradation. However, its use in quantifying acute changes has been limited due the low labeled peptide stoichiometry. Here, we describe the use of instrument logic to select peaks of interest via targeted mass differences (TMD) for overcoming this limitation. Comparing peptides artificially mixed at low heavy-to-light stoichiometry measured using standard data dependent acquisition with or without TMD revealed 2-3 fold increases in identification without significant loss in quantification precision for both MS2 and MS3 methods. Our benchmarked method approach increases throughput by reducing the necessary machine time. We anticipate that all pulsed SILAC measurements, if combined with TMT or not, would greatly benefit from instrument logic based approaches.
2020-05-29 | PXD018445 | Pride
Project description:Core regularity transcription factors (CR TFs) define cell identity and lineage through an exquisitely precise and logical order during embryogenesis and development. These CR TFs regulated one another in three-dimensional space via distal enhancers that serve as logic gates embedded in their TF recognition sequences. Aberrant chromatin organization resulting in miswired circuitry of enhancer logic is a newly recognized feature in many cancers. Here, we report that PAX3-FOXO1 expression is driven by a translocated FOXO1 distal super enhancer (SE). ChIP-seq in tumors bearing rare PAX translocations implicate enhancer miswiring is a pervasive feature across all FP-RMS tumors. Therefore, our data reveal a mechanism of a translocated hijacked enhancer which disrupts the normal CR TF logic during skeletal muscle development (PAX3 to MYOD to MYOG), replacing it with an infinite loop logic that makes rhabdomyosarcoma cells unable to exit the undifferentiated proliferating stage.
2019-12-25 | GSE136799 | GEO
Project description:Proof-of-concept for Mnase-SSP: a variant of Mnase-seq. Mnase-SSP dramatically increases the representation of short fragments of nucleolytically-digested DNA, enabling simultaneous analysis of transcription factor binding and nucleosome occupancy using the same assay. We used MNase-SSP to demarcate chromatin architecture at murine promoters and at transcription factor binding sites in murine embryonic stem cells. Are results reveal heterogeneity in the binding mode of C2H2 zinc fingers like Ctcf and Rest, demonstrating that Mnase-SSP, and SSP in general, as a flexible platform for profiling nucleolytically digested DNA for MNase-seq, MNase-ChIP, or CUT&RUN with reduced bias.
2019-02-12 | GSE125053 | GEO
Project description:Chromatin mapping using micrococcal nuclease (MNase) has been the standard tool for mapping nucleosomes for >40 years. When coupled with DNA sequencing, MNase-seq can provide base-pair-resolution nucleosome maps. However, determining nucleosome occupancy using MNase-seq has been hampered by its aggressive endo-/exo-nuclease activities, whereby cleavages within linker regions produce oligo- and mono-nucleosomes whereas cleavages within nucleosomes destroy them. Here we introduce a theoretical framework for predicting nucleosome occupancies and an experimental protocol with appropriate spike-in normalization that confirms our theory and provides accurate occupancy levels over an MNase digestion time-course. As expected, DNaseI hypersensitive sites and transcription units are digested by MNase at elevated rates, and the apparent deficiency of nucleosomes at 3’ ends of Drosophila genes is an artifact of MNase preference for AT-rich DNA. Surprisingly, we observed no overall differences between Drosophila euchromatin and heterochromatin, which implies that heterochromatin compaction does not render nucleosomal DNA less accessible than euchromatin.
2019-08-27 | GSE128689 | GEO