A high-throughput screening and computation platform for identifying synthetic promoters with enhanced cell-state specificity (SPECS)

Wu, Ming-Ru; Nissim, Lior; Stupp, Doron; Pery, Erez; Binder-Nissim, Adina; Weisinger, Karen; Enghuus, Casper; Palacios, Sebastian R.; Humphrey, Melissa; Zhang, Zhizhuo; Novoa, Eva Maria; Kellis, Manolis; Weiss, Ron; Rabkin, Samuel D.; Tabach, Yuval; Lu, Timothy K.

A high-throughput screening and computation platform for identifying synthetic promoters with enhanced cell-state specificity (SPECS)

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dc.contributor.author Wu, Ming-Ru
dc.contributor.author Nissim, Lior
dc.contributor.author Stupp, Doron
dc.contributor.author Pery, Erez
dc.contributor.author Binder-Nissim, Adina
dc.contributor.author Weisinger, Karen
dc.contributor.author Enghuus, Casper
dc.contributor.author Palacios, Sebastian R.
dc.contributor.author Humphrey, Melissa
dc.contributor.author Zhang, Zhizhuo
dc.contributor.author Novoa, Eva Maria
dc.contributor.author Kellis, Manolis
dc.contributor.author Weiss, Ron
dc.contributor.author Rabkin, Samuel D.
dc.contributor.author Tabach, Yuval
dc.contributor.author Lu, Timothy K.
dc.date.accessioned 2019-09-23T12:59:20Z
dc.date.available 2019-09-23T12:59:20Z
dc.date.issued 2019
dc.description.abstract Cell state-specific promoters constitute essential tools for basic research and biotechnology because they activate gene expression only under certain biological conditions. Synthetic Promoters with Enhanced Cell-State Specificity (SPECS) can be superior to native ones, but the design of such promoters is challenging and frequently requires gene regulation or transcriptome knowledge that is not readily available. Here, to overcome this challenge, we use a next-generation sequencing approach combined with machine learning to screen a synthetic promoter library with 6107 designs for high-performance SPECS for potentially any cell state. We demonstrate the identification of multiple SPECS that exhibit distinct spatiotemporal activity during the programmed differentiation of induced pluripotent stem cells (iPSCs), as well as SPECS for breast cancer and glioblastoma stem-like cells. We anticipate that this approach could be used to create SPECS for gene therapies that are activated in specific cell states, as well as to study natural transcriptional regulatory networks.
dc.format.mimetype application/pdf
dc.identifier.citation Wu MR, Nissim L, Stupp D, Pery E, Binder-Nissim A, Weisinger K, Enghuus C, Palacios SR, Humphrey M, Zhang Z, Maria Novoa E, Kellis M, Weiss R, Rabkin SD, Tabach Y, Lu TK. A high-throughput screening and computation platform for identifying synthetic promoters with enhanced cell-state specificity (SPECS). Nat Commun. 2019; 10(1): 2880. DOI 10.1038/s41467-019-10912-8
dc.identifier.doi http://dx.doi.org/10.1038/s41467-019-10912-8
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/42319
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nat Commun. 2019; 10(1): 2880
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Biotechnology
dc.subject.keyword Cancer
dc.subject.keyword Gene therapy
dc.subject.keyword Genetic engineering
dc.subject.keyword High-throughput screening
dc.title A high-throughput screening and computation platform for identifying synthetic promoters with enhanced cell-state specificity (SPECS)
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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