ChimeraUGEM: unsupervised gene expression modeling in any given organism

2019 ◽  
Vol 35 (18) ◽  
pp. 3365-3371 ◽  
Author(s):  
Alon Diament ◽  
Iddo Weiner ◽  
Noam Shahar ◽  
Shira Landman ◽  
Yael Feldman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Source Code ◽  
Software Tool ◽  
Supplementary Information ◽  
Host Organism ◽  
Protein Levels ◽  
Commercial Use ◽  
Sequence Patterns

Abstract Motivation Regulation of the amount of protein that is synthesized from genes has proved to be a serious challenge in terms of analysis and prediction, and in terms of engineering and optimization, due to the large diversity in expression machinery across species. Results To address this challenge, we developed a methodology and a software tool (ChimeraUGEM) for predicting gene expression as well as adapting the coding sequence of a target gene to any host organism. We demonstrate these methods by predicting protein levels in seven organisms, in seven human tissues, and by increasing in vivo the expression of a synthetic gene up to 26-fold in the single-cell green alga Chlamydomonas reinhardtii. The underlying model is designed to capture sequence patterns and regulatory signals with minimal prior knowledge on the host organism and can be applied to a multitude of species and applications. Availability and implementation Source code (MATLAB, C) and binaries are freely available for download for non-commercial use at http://www.cs.tau.ac.il/~tamirtul/ChimeraUGEM/, and supported on macOS, Linux and Windows. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals MoMo: Discovery of post-translational modification motifs

2017 ◽  
Author(s):  
Alice Cheng ◽  
Charles E. Grant ◽  
Timothy L. Bailey ◽  
William Stafford Noble
Keyword(s):  
Mass Spectrometry ◽  
Source Code ◽  
Software Tool ◽  
Mass Spectrometry Data ◽  
Supplementary Information ◽  
Biological Functions ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Sequence Patterns ◽  
Supplementary Material

AbstractMotivationPost-translational modifications (PTMs) of proteins are associated with many significant biological functions and can be identified in high throughput using tandem mass spectrometry. Many PTMs are associated with short sequence patterns called “motifs” that help localize the modifying enzyme. Accordingly, many algorithms have been designed to identify these motifs from mass spectrometry data.ResultsMoMo is a software tool for identifying motifs among sets of PTMs. The program re-implements two previously described algorithms, Motif-X and MoDL, packaging them in a web-accessible user interface. In addition to reading sequence files in FASTA format, MoMo is capable of directly parsing output files produced by commonly used mass spectrometry search engines. The resulting motifs are presented to the user in an HTML summary with motif logos and linked text files in MEME motif format.AvailabilitySource code and web server available at http://[email protected] and [email protected] informationSupplementary figures are available at Bioinformatics online.

scholarly journals TriPOINT: a software tool to prioritize important genes in pathways and their non-coding regulators

2018 ◽  
Vol 35 (15) ◽  
pp. 2686-2689
Author(s):  
Asa Thibodeau ◽  
Dong-Guk Shin
Keyword(s):  
Gene Expression ◽  
Software Tool ◽  
Supplementary Information ◽  
Analysis Tool ◽  
Graph Representations ◽  
Expression Levels ◽  
Conducting Pathway ◽  
Pathway Analysis Tool ◽  
Pathway Analyses ◽  
Gene Expression Levels

Abstract Summary Current approaches for pathway analyses focus on representing gene expression levels on graph representations of pathways and conducting pathway enrichment among differentially expressed genes. However, gene expression levels by themselves do not reflect the overall picture as non-coding factors play an important role to regulate gene expression. To incorporate these non-coding factors into pathway analyses and to systematically prioritize genes in a pathway we introduce a new software: Triangulation of Perturbation Origins and Identification of Non-Coding Targets. Triangulation of Perturbation Origins and Identification of Non-Coding Targets is a pathway analysis tool, implemented in Java that identifies the significance of a gene under a condition (e.g. a disease phenotype) by studying graph representations of pathways, analyzing upstream and downstream gene interactions and integrating non-coding regions that may be regulating gene expression levels. Availability and implementation The TriPOINT open source software is freely available at https://github.uconn.edu/ajt06004/TriPOINT under the GPL v3.0 license. Supplementary information Supplementary data are available at Bioinformatics online.

Mutants of cubitus interruptus that are independent of PKA regulation are independent of hedgehog signaling

Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3607-3616 ◽  
Author(s):  
Y. Chen ◽  
J.R. Cardinaux ◽  
R.H. Goodman ◽  
S.M. Smolik
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Ectopic Expression ◽  
Proteolytic Processing ◽  
Dominant Negative ◽  
Cubitus Interruptus ◽  
Target Gene Expression ◽  
Exogenous Expression

Hedgehog (HH) is an important morphogen involved in pattern formation during Drosophila embryogenesis and disc development. cubitus interruptus (ci) encodes a transcription factor responsible for transducing the hh signal in the nucleus and activating hh target gene expression. Previous studies have shown that CI exists in two forms: a 75 kDa proteolytic repressor form and a 155 kDa activator form. The ratio of these forms, which is regulated positively by hh signaling and negatively by PKA activity, determines the on/off status of hh target gene expression. In this paper, we demonstrate that the exogenous expression of CI that is mutant for four consensus PKA sites [CI(m1-4)], causes ectopic expression of wingless (wg) in vivo and a phenotype consistent with wg overexpression. Expression of CI(m1-4), but not CI(wt), can rescue the hh mutant phenotype and restore wg expression in hh mutant embryos. When PKA activity is suppressed by expressing a dominant negative PKA mutant, the exogenous expression of CI(wt) results in overexpression of wg and lethality in embryogenesis, defects that are similar to those caused by the exogenous expression of CI(m1-4). In addition, we demonstrate that, in cell culture, the mutation of any one of the three serine-containing PKA sites abolishes the proteolytic processing of CI. We also show that PKA directly phosphorylates the four consensus phosphorylation sites in vitro. Taken together, our results suggest that positive hh and negative PKA regulation of wg gene expression converge on the regulation of CI phosphorylation.

scholarly journals Electroporation-mediated delivery of catalytic oligodeoxynucleotides for manipulation of vascular gene expression

2003 ◽  
Vol 285 (5) ◽  
pp. H2240-H2247 ◽  
Author(s):  
Elizabeth A. Nunamaker ◽  
Hai-Ying Zhang ◽  
Yuichi Shirasawa ◽  
Joseph N. Benoit ◽  
David A. Dean
Keyword(s):  
Gene Expression ◽  
Experimental Studies ◽  
Wild Type ◽  
Protein Levels ◽  
Dna Oligonucleotides ◽  
Pkc Isoforms ◽  
Cell Layers ◽  
Cultured Smooth Muscle Cells ◽  
Decrease Gene Expression

The development of inexpensive and effective approaches to transiently decrease gene expression in vivo would be useful for the study of physiological processes in living animals. DNAzymes are a novel class of DNA oligonucleotides that can catalytically cleave target mRNAs and thereby reduce protein production. However, current methods for their delivery in vivo are limited and inefficient. In this study, we show that electroporation can be used to deliver DNAzymes to the intact mesenteric vasculature of rats. With the use of PKC-ϵ as a target, a set of wild-type and mutant control DNAzymes was designed and shown to reduce both PKC-ϵ mRNA and protein levels in cultured smooth muscle cells in a specific manner. The wild-type DNAzyme reduced PKC-ϵ protein levels by 70% at 24 h in two different cell lines without decreasing the levels of the five other PKC isoforms tested. When delivered to the intact vasculature using electroporation, the DNAzyme reduced PKC-ϵ protein levels by >60% without affecting these other PKC isoforms. Electroporation was required for oligonucleotide transfer and was able to deliver the DNAzymes to multiple cell layers in the vessel wall. Protein levels were reduced maximally by 24 h postelectroporation and returned to normal by 48 h. These results suggest that electroporation can be used to deliver DNAzymes and other DNA oligonucleotides to the vasculature in vivo and can decrease gene expression for a window of time that can be used for experimental studies.

255 THE ESTROGENIC EVALUATION OF PARABENS USING RAT UTERINE CALBINDIN-D9k

2010 ◽  
Vol 22 (1) ◽  
pp. 285
Author(s):  
T. T. B. Vo ◽  
E. B. Jeung
Keyword(s):  
Gene Expression ◽  
Adverse Effects ◽  
Treated Group ◽  
Environmental Chemicals ◽  
Female Rats ◽  
Protein Levels ◽  
Calbindin D9k ◽  
The Difference

In the current study, calbindin-D9k (CaBP-9k), a potent biomarker for screening estrogen-like environmental chemicals in vivo and in vitro, was adopted to examine the potential estrogen-like property of the following parabens: propyl-, isopropyl-, butyl-, and isobutyl-paraben. Immature female rats were administered for 3 days from postnatal day 14 to 16 with 17?-ethinylestradiol (EE, 1 mg/kg of body weight (BW) per day) or parabens (62.5, 250, and 1000 mg/kg of BW per day). In uterotrophic assays, significantly increased uterus weights were detected in the EE-treated group and in the groups treated with the greatest dose of isopropyl-, butyl- and isobutyl-paraben. In addition, these parabens induced uterine CaBP-9k mRNA and protein levels, whereas co-treatment of parabens and fulvestrant (Faslodex, formerly known as ICI 182, 780), a pure estrogen receptor (ER) antagonist, completely reversed the paraben-induced gene expression and increased uterine weights. To investigate the ER-mediated mechanism(s) by which parabens exert their effects, the expression level of ERα and progesterone receptor (PR) was analyzed. Exposure to EE or parabens caused a dramatic decrease in expression of both ER? mRNA and protein levels, whereas co-treatment with fulvestrant reversed these effects. These data showed the difference of CaBP-9k and ER? expression, suggesting that CaBP-9k might not express via ER? pathway. In the effect of parabens on CaBP-9k expression through PR mediation, a significantly increased expression of uterine PR gene, a well-known ER regulating gene, at both transcriptional and translational levels was indicated in the greatest dose of isopropyl- and butyl-paraben. These parabens induced PR gene expression that was completely blocked by fulvestrant. This result indicates that CaBP-9k expression might involve PR mediates in the estrogenic effect of paraben in immature rat uteri. Taken together, parabens exhibited an estrogen-like property in vivo, which might be mediated by a PR and/or ER? signaling pathway. In addition, our results expanded the current understanding of the potential adverse effects of parabens associated with their estrogen-like activities. Further investigation is needed to elucidate in greater detail the adverse effects of parabens in humans and wildlife.

scholarly journals MOLI: multi-omics late integration with deep neural networks for drug response prediction

2019 ◽  
Vol 35 (14) ◽  
pp. i501-i509 ◽  
Author(s):  
Hossein Sharifi-Noghabi ◽  
Olga Zolotareva ◽  
Colin C Collins ◽  
Martin Ester
Keyword(s):  
Gene Expression ◽  
Neural Networks ◽  
Prediction Accuracy ◽  
Drug Response ◽  
Deep Neural Networks ◽  
Response Prediction ◽  
Supplementary Information ◽  
Precision Oncology

Abstract Motivation Historically, gene expression has been shown to be the most informative data for drug response prediction. Recent evidence suggests that integrating additional omics can improve the prediction accuracy which raises the question of how to integrate the additional omics. Regardless of the integration strategy, clinical utility and translatability are crucial. Thus, we reasoned a multi-omics approach combined with clinical datasets would improve drug response prediction and clinical relevance. Results We propose MOLI, a multi-omics late integration method based on deep neural networks. MOLI takes somatic mutation, copy number aberration and gene expression data as input, and integrates them for drug response prediction. MOLI uses type-specific encoding sub-networks to learn features for each omics type, concatenates them into one representation and optimizes this representation via a combined cost function consisting of a triplet loss and a binary cross-entropy loss. The former makes the representations of responder samples more similar to each other and different from the non-responders, and the latter makes this representation predictive of the response values. We validate MOLI on in vitro and in vivo datasets for five chemotherapy agents and two targeted therapeutics. Compared to state-of-the-art single-omics and early integration multi-omics methods, MOLI achieves higher prediction accuracy in external validations. Moreover, a significant improvement in MOLI’s performance is observed for targeted drugs when training on a pan-drug input, i.e. using all the drugs with the same target compared to training only on drug-specific inputs. MOLI’s high predictive power suggests it may have utility in precision oncology. Availability and implementation https://github.com/hosseinshn/MOLI. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Hepatic gene expression patterns in thyroid hormone-treated hypothyroid rats

2003 ◽  
Vol 31 (2) ◽  
pp. 291-303 ◽  
Author(s):  
JM Weitzel ◽  
S Hamann ◽  
M Jauk ◽  
M Lacey ◽  
A Filbry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Activation Mechanism ◽  
Gene Expression Patterns ◽  
Peroxisome Proliferator ◽  
Gene Promoters ◽  
Protein Levels

Thyroid hormone (T3) is essential for normal development, differentiation and metabolic balance. We have performed DNA microarray experiments using hepatic RNA from hypothyroid and T3-treated hypothyroid rats in order to characterize T3-induced gene expression patterns after various time points (6, 24 and 48 h after the administration of the hormone). Sixty-two of 4608 different genes displayed a reproducible T3-response, and cluster analysis divided these differentially regulated genes into six expression patterns. Thirty-six genes were not significantly regulated within the first 24 h. Transient transfection experiments of eight late-induced gene promoters failed to detect a thyroid hormone response element within their regulatory elements, suggesting an indirect activation mechanism(s). In search for an intermediate factor of T3 action, we examined whether various rather ubiquitous transcription factors, peroxisome proliferator-activated receptors (PPARs) and coactivators of the PPARgamma coactivator 1 family (PGC-1) are regulated by T3. Only PPARgamma and PERC/PGC-1beta exhibit a significant T3-response within the first 6 h after treatment, identifying these factors as candidate components for mediating the late-induced expression pattern. Regulation of early-induced genes within the first 6 h after administration of T3 on transcript levels correlates with altered protein levels after 24 and 48 h in vivo.

CellTracker (not only) for dummies

2015 ◽  
Vol 32 (6) ◽  
pp. 955-957 ◽  
Author(s):  
Filippo Piccinini ◽  
Alexa Kiss ◽  
Peter Horvath
Keyword(s):  
Graphical User Interface ◽  
Open Source Software ◽  
Phase Contrast ◽  
Cell Tracking ◽  
Source Code ◽  
Software Tool ◽  
Time Lapse ◽  
Supplementary Information ◽  
Differential Interference Contrast ◽  
User Friendly

Abstract Motivation: Time-lapse experiments play a key role in studying the dynamic behavior of cells. Single-cell tracking is one of the fundamental tools for such analyses. The vast majority of the recently introduced cell tracking methods are limited to fluorescently labeled cells. An equally important limitation is that most software cannot be effectively used by biologists without reasonable expertise in image processing. Here we present CellTracker, a user-friendly open-source software tool for tracking cells imaged with various imaging modalities, including fluorescent, phase contrast and differential interference contrast (DIC) techniques. Availability and implementation: CellTracker is written in MATLAB (The MathWorks, Inc., USA). It works with Windows, Macintosh and UNIX-based systems. Source code and graphical user interface (GUI) are freely available at: http://celltracker.website/. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

scholarly journals Deubiquitinase USP47/UBP64E Regulates β-Catenin Ubiquitination and Degradation and Plays a Positive Role in Wnt Signaling

2015 ◽  
Vol 35 (19) ◽  
pp. 3301-3311 ◽  
Author(s):  
Jiandang Shi ◽  
Yajuan Liu ◽  
Xuehe Xu ◽  
Wen Zhang ◽  
Tianxin Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Interference ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
Target Gene ◽  
Central Question ◽  
Cancer Cell Growth ◽  
Positive Role ◽  
Content Type

Wnt signaling plays important roles in development and tumorigenesis. A central question about the Wnt pathway is the regulation of β-catenin. Phosphorylation of β-catenin by CK1α and GSK3 promotes β-catenin binding to β-TrCP, leading to β-catenin degradation through the proteasome. The phosphorylation and ubiquitination of β-catenin have been well characterized; however, it is unknown whether and how a deubiquitinase is involved. In this study, by screening RNA interference (RNAi) libraries, we identified USP47 as a deubiquitinase that prevents β-catenin ubiquitination. Inactivation of USP47 by RNAi increased β-catenin ubiquitination, attenuated Wnt signaling, and repressed cancer cell growth. Furthermore, USP47 deubiquitinates itself, whereas β-TrCP promotes USP47 ubiquitination through interaction with an atypical motif in USP47. Finally,in vivostudies in theDrosophilawing suggest that UBP64E, the USP47 counterpart inDrosophila, is required for Armadillo stabilization and plays a positive role in regulating Wnt target gene expression.

scholarly journals The receptor-like cytoplasmic kinase MAZZA and CLAVATA-family receptors interact in vivo, together mediating developmental processes in Arabidopsis thaliana

2020 ◽  
Author(s):  
Patrick Blümke ◽  
Jenia Schlegel ◽  
Sabine Becher ◽  
Karine Pinto ◽  
Rüdiger Simon
Keyword(s):  
Gene Expression ◽  
Arabidopsis Thaliana ◽  
Plasma Membrane ◽  
Root Development ◽  
Target Gene ◽  
Size Control ◽  
Receptor Complexes ◽  
Cle Peptide ◽  
Developmental Contexts

AbstractThe receptor-like kinases (RLKs) CLAVATA1 (CLV1) and BARELY ANY MERISTEMs (BAM1 – 3) form the CLV-family (CLVf), which perceives peptides of the CLV3/EMBRYO SURROUNDING REGION (ESR)-related (CLE) family within various signaling pathways of Arabidopsis thaliana. CLE peptide signaling, which is required for meristem size control, vascular development, or pathogen responses, involves the formation of receptor complexes at the plasma membrane (PM). These complexes comprise RLKs and co-receptors in varying compositions depending on the signaling context and regulate target gene expression, such as WUSCHEL (WUS). How the CLE signal is transmitted intracellularly after perception at the PM is not known.Here, we found that the membrane-associated receptor-like cytoplasmic kinase (RLCK) MAZZA (MAZ) MAZ and additional members of the Pti1-like protein family interact in vivo with CLVf receptors. MAZ, which is widely expressed throughout the plant, localizes to the PM via posttranslational palmitoylation potentially enabling stimulus-triggered protein re-localization. We identified a role for a CLV1/MAZ signaling module during stomatal and root development, and redundancy could potentially mask other phenotypes of maz-1 mutants. We propose that RLCKs such as MAZ mediate CLVf signaling in a variety of developmental contexts, paving the way towards understanding the intracellular processes after CLE peptide perception.

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