scholarly journals Kinetic modeling of stem cell transcriptome dynamics to identify regulatory modules of normal and disturbed neuroectodermal differentiation

2020 ◽  
Vol 48 (22) ◽  
pp. 12577-12592
Author(s):  
Johannes Meisig ◽  
Nadine Dreser ◽  
Marion Kapitza ◽  
Margit Henry ◽  
Tamara Rotshteyn ◽  
...  
Keyword(s):  
Data Sets ◽  
Beta Catenin ◽  
Transcriptome Data ◽  
Time Resolved ◽  
Regulatory Modules ◽  
Dynamic Cell ◽  
Gene Expression Dynamics ◽  
Cell Transcriptome ◽  
Response Modelling ◽  
Phenotypic Rescue

Abstract Thousands of transcriptome data sets are available, but approaches for their use in dynamic cell response modelling are few, especially for processes affected simultaneously by two orthogonal influencing variables. We approached this problem for neuroepithelial development of human pluripotent stem cells (differentiation variable), in the presence or absence of valproic acid (signaling variable). Using few basic assumptions (sequential differentiation states of cells; discrete on/off states for individual genes in these states), and time-resolved transcriptome data, a comprehensive model of spontaneous and perturbed gene expression dynamics was developed. The model made reliable predictions (average correlation of 0.85 between predicted and subsequently tested expression values). Even regulations predicted to be non-monotonic were successfully validated by PCR in new sets of experiments. Transient patterns of gene regulation were identified from model predictions. They pointed towards activation of Wnt signaling as a candidate pathway leading to a redirection of differentiation away from neuroepithelial cells towards neural crest. Intervention experiments, using a Wnt/beta-catenin antagonist, led to a phenotypic rescue of this disturbed differentiation. Thus, our broadly applicable model allows the analysis of transcriptome changes in complex time/perturbation matrices.

scholarly journals Selective time-dependent changes of Cu(DPPE)(DMP)·PF6on photoexcitation

2014 ◽  
Vol 70 (a1) ◽  
pp. C776-C776 ◽  
Author(s):  
Elzbieta Trzop ◽  
Bertrand Fournier ◽  
Katarzyna Jarzembska ◽  
Jesse Sokolow ◽  
Radoslaw Kaminski ◽  
...  
Keyword(s):  
Structural Changes ◽  
Dye Sensitized Solar Cells ◽  
Department Of Energy ◽  
Data Sets ◽  
Monoclinic System ◽  
Time Resolved ◽  
Pump Probe ◽  
Light Emitting Devices ◽  
Potential Applications ◽  
Photon Source

Thanks to their potential applications as light-emitting devices, chemical sensors and dye-sensitized solar cells, heteroleptic copper (I) complexes have been extensively studied. Cu(DPPE)(DMP)·PF6(dppe= 1,2-bis(diphenylphosphino)ethane; dmp = 2,9-dimethyl-1,10-phenanthroline) crystallizes in the monoclinic system, P21/c, with two independent molecules in the asymmetric unit. Previous studies on this system [1,2] show strong temperature-dependent emission. The complex was studied at 90K under 355nm laser excitation. At this temperature, the luminescence decay for Cu(DPPE)(DMP)·PF6is biexponential with lifetimes of ~3μs and ~28μs. Two time-resolved X-ray diffraction techniques were applied for studies: (1) a Laue technique at BioCARS ID-14 beamline at the Advanced Photon Source, and (2) monochromatic diffraction at a newly constructed in-house pump-probe monochromatic facility at the University at Buffalo. Structural changes determined with the two methods are in qualitative agreement; discrepancies in position of the Cu and P atoms were observed. The molecular distortions were smaller than those determined at 16K in the earlier synchrotron study by Vorontsov et al. [2]. Photodeformation maps (see Figure below), in which the increase in temperature on photoexcitation has been eliminated, clearly illustrate the photoinduced atomic shifts for both data sets. Results will be compared with those obtained for other studied heteroleptic copper (I) complexes, for instance Cu[(1,10-phenanthroline-N,N′) bis(triphenylphosphine)]·BF4[3]. The in-house pump-probe facility is discussed by Radoslaw Kaminski at this meeting. Research funded by the National Science Foundation (CHE1213223). BioCARS Sector 14 at APS is supported by NIH (RR007707). The Advanced Photon Source is funded by the Office of Basic Energy Sciences, U.S. Department of Energy, (W-31-109-ENG-38). KNJ is supported by the Polish Ministry of Science and Higher Education through the "Mobility Plus" program.

Feature Extraction From Time Resolved Reacting Flow Data Sets

2018 ◽  
Author(s):  
H. Ek ◽  
I. Chterev ◽  
N. Rock ◽  
B. Emerson ◽  
J. Seitzman ◽  
...  
Keyword(s):  
Swirling Flow ◽  
Azimuthal Velocity ◽  
Flow Fields ◽  
Swirl Flow ◽  
Reacting Flow ◽  
Data Sets ◽  
Time Resolved ◽  
Recirculating Flow ◽  
Flow Features ◽  
Dynamical Flow

This paper presents measurements of the simultaneous fuel distribution, flame position and flow velocity in a high pressure, liquid fueled combustor. Its objective is to develop methods to process, display and compare large quantities of instantaneous data with computations. However, time-averaged flow fields rarely represent the instantaneous, dynamical flow fields in combustion systems. It is therefore important to develop methods that can algorithmically extract dynamical flow features and be directly compared between measurements and computations. While a number of data-driven approaches have been previously presented in the literature, the purpose of this paper is to propose several approaches that are based on understanding of key physical features of the flow — for this reacting swirl flow, these include the annular jet, the swirling flow which may be precessing, the recirculating flow between the annular jets, and the helical flow structures in the shear layers. This paper demonstrates nonlinear averaging of axial and azimuthal velocity profiles, which provide insights into the structure of the recirculation zone and degree of flow precession. It also presents probability fields for the location of vortex cores that enables a convenient method for comparison of their trajectory and phasing with computations. Taken together, these methods illustrate the structure and relative locations of the annular fluid jet, recirculating flow zone, spray location, flame location, and trajectory of the helical vortices.

scholarly journals New processing tools for weak and/or spatially overlapped macromolecular diffraction patterns

1999 ◽  
Vol 55 (10) ◽  
pp. 1733-1741 ◽  
Author(s):  
Dominique Bourgeois
Keyword(s):  
Signal To Noise Ratio ◽  
Data Sets ◽  
Signal To Noise ◽  
Weighting Method ◽  
Time Resolved ◽  
Accurate Evaluation ◽  
Profile Fitting ◽  
Integration Program ◽  
Diffraction Patterns ◽  
New Processing

Tools originally developed for the treatment of weak and/or spatially overlapped time-resolved Laue patterns were extended to improve the processing of difficult monochromatic data sets. The integration programPrOWallows deconvolution of spatially overlapped spots which are usually rejected by standard packages. By using dynamically adjusted profile-fitting areas, a carefully built library of reference spots and interpolation of reference profiles, this program also provides a more accurate evaluation of weak spots. In addition, by using Wilson statistics, it allows rejection of non-redundant strong outliers such as zingers, which otherwise may badly corrupt the data. A weighting method for optimizing structure-factor amplitude differences, based on Bayesian statistics and originally applied to low signal-to-noise ratio time-resolved Laue data, is also shown to significantly improve other types of subtle amplitude differences, such as anomalous differences.

scholarly journals Identification of Macrophage Genotype and Key Biological Pathways in Circulating Angiogenic Cell Transcriptome

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Bert R. Everaert ◽  
Steven J. Van Laere ◽  
Robrecht Lembrechts ◽  
Vicky Y. Hoymans ◽  
Jean-Pierre Timmermans ◽  
...  
Keyword(s):  
Cytokine Expression ◽  
Retinoid X Receptor ◽  
Farnesoid X Receptor ◽  
Data Sets ◽  
Cytokine Expression Profile ◽  
Pathways Analysis ◽  
Show Evidence ◽  
Cell Transcriptome ◽  
And Function

Background. Circulating angiogenic cells (CAC) have been identified as important regulators of vascular biology. However, there is still considerable debate about the genotype and function of CAC. Methods and Results. Data from publicly available gene expression data sets were used to analyse the transcriptome of in vitro cultured CAC (CACiv). Genes and pathways of interest were further evaluated using qPCR comparing CACiv versus CD14+ monocytic cells. The CACiv transcriptome strongly related to tissue macrophages, and more specifically to regulatory M2c macrophages. The cytokine expression profile of CACiv was predominantly immune modulatory and resembled the cytokine expression of tumor-associated macrophages (TAM). Pathway analysis revealed previously unrecognized biological processes in CACiv, such as riboflavin metabolism and liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor (FXR)/retinoid X receptor (RXR) pathways. Analysis of endothelial-specific genes did not show evidence for endothelial transdifferentiation. Conclusions. CACiv are genotypically similar to regulatory M2c macrophages and lack signs of endothelial differentiation.

scholarly journals Targeting Subsets of Mammalian Neurons

2020 ◽  
Vol 15 ◽  
pp. 263310552090853
Author(s):  
Boris V. Zemelman
Keyword(s):  
In Vivo Imaging ◽  
Inhibitory Neuron ◽  
Human Perception ◽  
Cell Populations ◽  
Inhibitory Interneurons ◽  
Transcriptome Data ◽  
Functional Studies ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Functional dissection of mammalian neuronal circuits depends on accurate targeting of constituent cell classes. Transgenic mice offer precise and predictable access to genetically defined cell populations, but there is the pressing need to target neuronal assemblies in species less amenable to genomic manipulations, such as the primate, which is an important animal model for human perception, cognition, and action. We have developed several virus-based methods for accessing all forebrain inhibitory interneurons as well as the major excitatory and inhibitory neuron subclasses. These methods rely on the wealth of emerging single-cell transcriptome data and harness gene expression variations to refine neuron targeting. Our approach enables nuanced functional studies, including in vivo imaging and manipulation, of the diverse cell populations of the mammalian neocortex, and it represents a timely blueprint for transgenics-independent interrogation of functionally significant cell classes.

scholarly journals Dynamics of Cardiac Neutrophil Diversity in Murine Myocardial Infarction

2020 ◽  
Vol 127 (9) ◽  
Author(s):  
Ehsan Vafadarnejad ◽  
Giuseppe Rizzo ◽  
Laura Krampert ◽  
Panagiota Arampatzi ◽  
Anahi-Paula Arias-Loza ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Bone Marrow ◽  
Single Cell ◽  
Ischemic Heart ◽  
Time Resolved ◽  
Tissue Healing ◽  
Receptor Interactions ◽  
Blood Neutrophils ◽  
Gene Expression Dynamics

Rationale: After myocardial infarction, neutrophils rapidly and massively infiltrate the heart, where they promote both tissue healing and damage. Objective: To characterize the dynamics of circulating and cardiac neutrophil diversity after infarction. Methods and results: We employed single-cell transcriptomics combined with cell surface epitope detection by sequencing to investigate temporal neutrophil diversity in the blood and heart after murine myocardial infarction. At day 1, 3, and 5 after infarction, cardiac Ly6G + (lymphocyte antigen 6G) neutrophils could be delineated into 6 distinct clusters with specific time-dependent patterning and proportions. At day 1, neutrophils were characterized by a gene expression profile proximal to bone marrow neutrophils ( Cd177 , Lcn2 , Fpr1 ), and putative activity of transcriptional regulators involved in hypoxic response ( Hif1a ) and emergency granulopoiesis ( Cebpb ). At 3 and 5 days, 2 major subsets of Siglecf hi (enriched for eg, Icam1 and Tnf ) and Siglecf low ( Slpi, Ifitm1 ) neutrophils were found. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) analysis in blood and heart revealed that while circulating neutrophils undergo a process of aging characterized by loss of surface CD62L and upregulation of Cxcr4 , heart infiltrating neutrophils acquired a unique SiglecF hi signature. SiglecF hi neutrophils were absent from the bone marrow and spleen, indicating local acquisition of the SiglecF hi signature. Reducing the influx of blood neutrophils by anti-Ly6G treatment increased proportions of cardiac SiglecF hi neutrophils, suggesting accumulation of locally aged neutrophils. Computational analysis of ligand/receptor interactions revealed putative pathways mediating neutrophil to macrophage communication in the myocardium. Finally, SiglecF hi neutrophils were also found in atherosclerotic vessels, revealing that they arise across distinct contexts of cardiovascular inflammation. Conclusions: Altogether, our data provide a time-resolved census of neutrophil diversity and gene expression dynamics in the mouse blood and ischemic heart at the single-cell level, and reveal a process of local tissue specification of neutrophils in the ischemic heart characterized by the acquisition of a SiglecF hi signature.

scholarly journals CoMM: A Collaborative Mixed Model That Integrates GWAS and eQTL Data Sets to Investigate the Genetic Architecture of Complex Traits

2019 ◽  
Vol 13 ◽  
pp. 117793221988143 ◽  
Author(s):  
Kar-Fu Yeung ◽  
Yi Yang ◽  
Can Yang ◽  
Jin Liu
Keyword(s):  
Gene Expression ◽  
Association Study ◽  
Genetic Variants ◽  
Complex Traits ◽  
Mixed Model ◽  
Genome Wide Association Study ◽  
Data Sets ◽  
Transcriptome Data ◽  
Data Set ◽  
Expression Levels

Genome-wide association study (GWAS) analyses have identified thousands of associations between genetic variants and complex traits. However, it is still a challenge to uncover the mechanisms underlying the association. With the growing availability of transcriptome data sets, it has become possible to perform statistical analyses targeted at identifying influential genes whose expression levels correlate with the phenotype. Methods such as PrediXcan and transcriptome-wide association study (TWAS) use the transcriptome data set to fit a predictive model for gene expression, with genetic variants as covariates. The gene expression levels for the GWAS data set are then ‘imputed’ using the prediction model, and the imputed expression levels are tested for their association with the phenotype. These methods fail to account for the uncertainty in the GWAS imputation step, and we propose a collaborative mixed model (CoMM) that addresses this limitation by jointly modelling the multiple analysis steps. We illustrate CoMM’s ability to identify relevant genes in the Northern Finland Birth Cohort 1966 data set and extend the model to handle the more widely available GWAS summary statistics.

scholarly journals New Phylogenomic Analysis of the Enigmatic Phylum Telonemia Further Resolves the Eukaryote Tree of Life

2019 ◽  
Vol 36 (4) ◽  
pp. 757-765 ◽  
Author(s):  
Jürgen F H Strassert ◽  
Mahwash Jamy ◽  
Alexander P Mylnikov ◽  
Denis V Tikhonenkov ◽  
Fabien Burki
Keyword(s):  
Phylogenetic Signal ◽  
Evolutionary Origin ◽  
Phylogenetic Position ◽  
Aquatic Environments ◽  
Phylogenomic Analysis ◽  
Data Sets ◽  
Transcriptome Data ◽  
Phylogenetic Reconstructions ◽  
Phylogenomic Analyses ◽  
Alignment Length

AbstractThe resolution of the broad-scale tree of eukaryotes is constantly improving, but the evolutionary origin of several major groups remains unknown. Resolving the phylogenetic position of these “orphan” groups is important, especially those that originated early in evolution, because they represent missing evolutionary links between established groups. Telonemia is one such orphan taxon for which little is known. The group is composed of molecularly diverse biflagellated protists, often prevalent although not abundant in aquatic environments. Telonemia has been hypothesized to represent a deeply diverging eukaryotic phylum but no consensus exists as to where it is placed in the tree. Here, we established cultures and report the phylogenomic analyses of three new transcriptome data sets for divergent telonemid lineages. All our phylogenetic reconstructions, based on 248 genes and using site-heterogeneous mixture models, robustly resolve the evolutionary origin of Telonemia as sister to the Sar supergroup. This grouping remains well supported when as few as 60% of the genes are randomly subsampled, thus is not sensitive to the sets of genes used but requires a minimal alignment length to recover enough phylogenetic signal. Telonemia occupies a crucial position in the tree to examine the origin of Sar, one of the most lineage-rich eukaryote supergroups. We propose the moniker “TSAR” to accommodate this new mega-assemblage in the phylogeny of eukaryotes.

Sign in / Sign up

Export Citation Format

Share Document