Project description:We investigate how a protein-protein interaction between two ancient transcriptional regulators (a homeodomain and MADS box protein) was gained approximately 200 million years ago in a clade of ascomycete yeasts that includes Saccharomyces cerevisiae. We combine deep mutational scanning of Matα2 with a functional selection for cooperative gene expression and tested millions of possible alternative evolutionary solutions to this interaction interface. Pooled Matα2 mutants were deeply sequenced before and after selection for functional Matα2-Mcm1 interaction. The changes in frequency of each variant allowed us to determine their relative fitness.
Project description:This is a prospective, multicenter, randomized study to evaluate the clinical performance of a novel CADe device, WISE VISION Endoscopy System, in patients undergoing high-definition white light (HDWL) colonoscopy for screening or surveillance of colorectal Cancer (CRC).
Eligible subjects who meet the study inclusion/exclusion criteria will be randomized in a 1:1 ratio to undergo colonoscopy :
* Experimental: CADe colonoscopy procedure with WISE VISION Endoscopy (CADe Group)
* Control: Standard Colonoscopy without CADe (Standard Colonoscopy Group)
Project description:The aim of this study was to develop an organ wise proteome map for Labeo rohita. Using LC-MS/MS, we have performed in-depth proteomics analysis of 19 different sample types, including 17 tissue samples, plasma from female fish and embryo 4-day post fertilization. Whole analysis resulted in the identification of more than more than 8000 proteins with 1% FDR of which more than 76% were identified with two or more than two unique peptides. The dataset show organ wise pattern of protein expression along with extensive catalogue of orgsn wise Post translational modification. This proteomic information would complement the recently published genome to accelerate further research.
Project description:Informative gene selection can have important implications for the improvement of cancer diagnosis and the identification of new drug targets. Individual-gene-ranking methods ignore interactions between genes. Furthermore, popular pair-wise gene evaluation methods, e.g. TSP and TSG, are helpless for discovering pair-wise interactions. Several efforts to discover pair-wise synergy have been made based on the information approach, such as EMBP and FeatKNN. However, the methods which are employed to estimate mutual information, e.g. binarization, histogram-based and KNN estimators, depend on known data or domain characteristics. Recently, Reshef et al. proposed a novel maximal information coefficient (MIC) measure to capture a wide range of associations between two variables that has the property of generality. An extension from MIC(X; Y) to MIC(X1; X2; Y) is therefore desired. We developed an approximation algorithm for estimating MIC(X1; X2; Y) where Y is a discrete variable. MIC(X1; X2; Y) is employed to detect pair-wise synergy in simulation and cancer microarray data. The results indicate that MIC(X1; X2; Y) also has the property of generality. It can discover synergic genes that are undetectable by reference feature selection methods such as MIC(X; Y) and TSG. Synergic genes can distinguish different phenotypes. Finally, the biological relevance of these synergic genes is validated with GO annotation and OUgene database.
Project description:P53 wildtype or complementing DNA binding cooperativity versions (p53EE, p53RR, p53EE/RR) were overexpressed in SAOS cells. After 18h cells were harvested and subjected to expression profiling.
Project description:p53 wildtype or complementing DNA binding cooperativity versions (EE, RR, EE/RR) were overexpressed in SAOS cells and 18h later harvested to perform ChIP with an p53-specific antibody. The enriched DNA fragments were purified and identified by high throughput sequencing.
Project description:Transcription factors (TFs) can define distinct cellular identities despite nearly identical DNA-binding specificities. One mechanism for achieving regulatory specificity is DNA-guided TF cooperativity. Although in vitro studies suggest it may be common, examples of such cooperativity remain scarce in cellular contexts. Here, we demonstrate how ‘Coordinator’, a long DNA motif comprised of common motifs bound by many basic helix-loop-helix (bHLH) and homeodomain (HD) TFs, uniquely defines regulatory regions of embryonic face and limb mesenchyme. Coordinator guides cooperative and selective binding between the bHLH family mesenchymal regulator TWIST1 and a collective of HD factors associated with regional identities in the face and limb. TWIST1 is required for HD binding and open chromatin at Coordinator sites, while HD factors stabilize TWIST1 occupancy at Coordinator and titrate it away from HD-independent sites. This cooperativity results in shared regulation of genes involved in cell-type and positional identities, and ultimately shapes facial morphology and evolution.
Project description:Transcription factors (TFs) can define distinct cellular identities despite nearly identical DNA-binding specificities. One mechanism for achieving regulatory specificity is DNA-guided TF cooperativity. Although in vitro studies suggest it may be common, examples of such cooperativity remain scarce in cellular contexts. Here, we demonstrate how ‘Coordinator’, a long DNA motif comprised of common motifs bound by many basic helix-loop-helix (bHLH) and homeodomain (HD) TFs, uniquely defines regulatory regions of embryonic face and limb mesenchyme. Coordinator guides cooperative and selective binding between the bHLH family mesenchymal regulator TWIST1 and a collective of HD factors associated with regional identities in the face and limb. TWIST1 is required for HD binding and open chromatin at Coordinator sites, while HD factors stabilize TWIST1 occupancy at Coordinator and titrate it away from HD-independent sites. This cooperativity results in shared regulation of genes involved in cell-type and positional identities, and ultimately shapes facial morphology and evolution.
Project description:Transcription factors (TFs) can define distinct cellular identities despite nearly identical DNA-binding specificities. One mechanism for achieving regulatory specificity is DNA-guided TF cooperativity. Although in vitro studies suggest it may be common, examples of such cooperativity remain scarce in cellular contexts. Here, we demonstrate how ‘Coordinator’, a long DNA motif comprised of common motifs bound by many basic helix-loop-helix (bHLH) and homeodomain (HD) TFs, uniquely defines regulatory regions of embryonic face and limb mesenchyme. Coordinator guides cooperative and selective binding between the bHLH family mesenchymal regulator TWIST1 and a collective of HD factors associated with regional identities in the face and limb. TWIST1 is required for HD binding and open chromatin at Coordinator sites, while HD factors stabilize TWIST1 occupancy at Coordinator and titrate it away from HD-independent sites. This cooperativity results in shared regulation of genes involved in cell-type and positional identities, and ultimately shapes facial morphology and evolution.