Find research datasets worth reusing

opencc-by-4.0Feb 2023View details →

Sachs: Protein and Phospholipids Expressions

The Sachs dataset measures the expression level of different proteins and phospholipids in human cells. It includes the simultaneous measurements of 11 phosphorylated proteins and phospholipids derived from thousands of individual primary immune system cells, subjected to both general and specific molecular interventions.   Task: The dataset can be used to study causal discovery algorithms.   Summary:  <ul> <li>Size of collection: 14 datasets on 11 features and 707 to 927 observations</li> <li>Task: Causal Discovery Problem</li> <li>Data Type: Continuous Data</li> <li>Dataset Scope: Collection of Datasets</li> <li>Ground Truth: Known Graph</li> <li>Temporal Structure: Static Data</li> <li>License: CC BY (granted by G. Nolan and D. Lauffenburger)</li> <li>Missing Values: No Missing Data</li> </ul>   Missingness Statement: There are no missing values.   Features: Each sample in each dataset consists of quantitative amounts of each of the following 11 phosphorylated molecules, simultaneously measured from single cells: <table> <tbody> <tr> <th>Measured molecule</th> <th>Antibody specificity</th> </tr> </tbody> <tbody> <tr> <td>Raf</td> <td>Phosphorylation at S259</td> </tr> <tr> <td>Erk1 and Erk2</td> <td>Phosphorylation at T202 and Y204</td> </tr> <tr> <td>P38</td> <td>Phosphorylation at T180 and Y182</td> </tr> <tr> <td>Jnk</td> <td>Phosphorylation at T183 and Y185</td> </tr> <tr> <td>Akt.</td> <td>Phosphorylation at S473</td> </tr> <tr> <td>Mek 1 and Mek2</td> <td>Phosphorylation at S217 and S221</td> </tr> <tr> <td>PKA substrates</td> <td>Detects proteins and peptides containing a phospho-Ser/Thr residue with arginine at the -3 position</td> </tr> <tr> <td>PKC</td> <td>Detects phosphorylated PKC-α, -βI, -βII, -δ, -ϵ, -η, and -θ isoforms only at C-terminal residue homologous to S660 of PKC-βII</td> </tr> <tr> <td>Plcg</td> <td>Phosphorylation at Y783</td> </tr> <tr> <td>PIP2</td> <td>Detects PIP2</td> </tr> <tr> <td>PIP3</td> <td>Detects PIP3</td> </tr> </tbody> </table>   Files: The datasets were collected after a series of stimulatory cues and inhibitory interventions, with cell reactions stopped at 15 minutes after stimulation by fixation, to profile the effects of each condition on the intracellular signaling networks of human primary naïve CD4+ T cells, downstream of CD3, CD28, and LFA-1 activation. The following conditions were used: <table> <tbody> <tr> <th>File</th> <th>Stimulation</th> <th>Description</th> </tr> </tbody> <tbody> <tr> <td>cd3cd28.csv</td> <td>CD3, CD28</td> <td>T cell activation</td> </tr> <tr> <td>cd3cd28icam2.csv</td> <td>CD3, CD28, ICAM-2</td> <td>LFA-1 signaling induction</td> </tr> <tr> <td>cd3cd28_aktinhib.csv</td> <td>CD3, CD28, akt-inhibitor</td> <td>PKA activation</td> </tr> <tr> <td>cd3cd28_g0076.csv</td> <td>CD3, CD28, G0076</td> <td>AKT inhibition</td> </tr> <tr> <td>cd3cd28_psitect.csv</td> <td>CD3, CD28, Psitectorigenin</td> <td>MEK1/MEK2 inhibition</td> </tr> <tr> <td>cd3cd28_u0126.csv</td> <td>CD3, CD28, U0126</td> <td>PKC activation</td> </tr> <tr> <td>cd3cd28_ly.csv</td> <td>CD3, CD28, LY294002</td> <td>PKC inhibition</td> </tr> <tr> <td>pma.csv</td> <td>PMA</td> <td>PIP2 production inhibition</td> </tr> <tr> <td>b2camp.csv</td> <td>β2camp</td> <td>AKT inhibition</td> </tr> <tr> <td>cd3cd28icam2_aktinhib.csv</td> <td>CD3, CD28, ICAM-2, akt-inhib</td> <td>simulated dataset</td> </tr> <tr> <td>cd3cd28icam2_g0076.csv</td> <td>CD3, CD28, ICAM-2, G0076</td> <td>simulated dataset</td> </tr> <tr> <td>cd3cd28icam2_psit.csv</td> <td>CD3, CD28, ICAM-2, Psitectorigenin</td> <td>simulated dataset</td> </tr> <tr> <td>cd3cd28icam2_u0126.csv</td> <td>CD3, CD28, ICAM-2, U0126</td> <td>simulated dataset</td> </tr> <tr> <td>cd3cd28icam2_ly.csv</td> <td>CD3, CD28, ICAM-2, LY294002</td> <td>simulated dataset</td> </tr> </tbody> </table> <ul> <li>Ground_Truth.csv: Directed Graph derived in Sachs et al. (2005) through multiple interventional experiments.</li> </ul>

opencc-by-4.0Mar 2023View details →

Venusian bow shock crossings manually identified from measurements by the ASPERA-4 and MAG instruments onboard Venus Express

Bow shock crossings at Venus identified manually from the ASPERA-4 and MAG instruments onboard Venus Express for the full mission from 2006 to 2014. A detailed description of the dataset can be found in the paper "Influence of solar wind variations on the shapes of Venus’ plasma boundaries based on Venus Express observations" by Signoles et al. The boundary crossings by Venus Express are determined from combining the measurements of both ion, electron and magnetic field measurements. The bow shock is identified from the sharp increase in the magnetic field magnitude, and the increase in electron and ion temperature. The ion composition boundary is identified from the decrease in magnetosheath protons and electrons, and the appearance of planetary heavy ions. The dataset contains 5193 identified bow shock crossings and 2679 identified ion composition boundary crossings. For more information on the dataset contact: M. Persson, moaperssonphd at gmail.com

opencc-zeroMar 2023View details →

Data from: Fungal symbionts generate water-saver and water-spender plant drought strategies via diverse effects on host gene expression

Panicum hallii var hallii HAL2 plants were inoculated individually with six foliar fungal endophytes or fungus-free controls and subjected to 5% or 20% soil moisture treatments. The fungi were selected for their previously observed effects on plant drought physiology, inducing either a "water saver" or a "water spender" strategy in the host. Plants were grown in enclosed microcosms to prevent cross-contamination and each treatment and control included 6 replicates. All fungi were Ascomycetes isolated from plants in central Texas. Plants were monitored for height, wilt, water loss, and survival. At the harvest, we also measured biomass and leaf colonization by the fungi and flash-froze leaf tissue for transcriptomic analyses. Both plant response and gene expression data are provided.

opencc-by-4.0Sep 2016View details →

A benchmark of gene expression tissue-specificity metrics

Supplementary figures and data to the paper "A benchmark of gene expression tissue-specificity metrics" Briefings in Bioinformatics, Volume 18, Issue 2, March 2017, Pages 205–214, <a href="https://doi.org/10.1093/bib/bbw008">https://doi.org/10.1093/bib/bbw008</a> Previously published at FigShare, republishing because of access problems for some researchers.

opencc-zeroApr 2023View details →

Data for: Weaker selection on genes with treatment-specific expression consistent with a limit on plasticity evolution in Arabidopsis thaliana

Differential gene expression between environments often underlies phenotypic plasticity. However, environment-specific expression patterns are hypothesized to relax selection on genes, and thus limit plasticity evolution. We collated over 27 terabases of RNA-sequencing data on Arabidopsis thaliana from over 300 peer-reviewed studies and 200 treatment conditions to investigate this hypothesis. Consistent with relaxed selection, genes with more treatment-specific expression have higher levels of nucleotide diversity and divergence at nonsynonymous sites but lack stronger signals of positive selection. This result persisted even after controlling for expression level, gene length, GC content, the tissue specificity of expression, and technical variation between studies. Overall, our investigation supports the existence of a hypothesized trade-off between the environment specificity of a gene's expression and the strength of selection on said gene in A. thaliana. Future studies should leverage multiple genome-scale datasets to tease apart the contributions of many variables in limiting plasticity evolution.

opencc-by-4.0Apr 2023View details →

Set of Data from "Selective targeting of striatal parvalbumin-expressing interneurons for transgene delivery" https://doi.org/10.1016/j.jneumeth.2021.109105

PVCre (+/+) mice were injected in the right striatum with AAV2/1-hsyn-FLEX-eGFP AAV2/9-CBA-FLEX-eGFP  or AAV2/9-hsyn-FLEX-eGFP vectors. Two weeks after, cells were manually counted by a blind observer on 2D maximal intensity projections of confocal images transformed into the tiff format using the Multi-point tool in ImageJ. The GraphPad .pzfx files show the quantitative anaylsis of the proportion of GFP+ cells which were PV+ (specificty) , the proportion of PV+ cells which were GFP+ (efficiency), the proportion of PV+ cells in the injected striatum relative to to the injected striatum of PVCre (+/+) mice (absence of vector toxicity) and the proportion of PV+ cells in the striatum  of PVCre (+/+) mice versus wt mice.

RNAseq data: Analysis of circRNA expression in human neuronal differentiation

This dataset contains sequencing read count data related to samples from differentiating human neuroepithelial stem cells (NES) collected at days zero (NES), five (D5) and 28 (D28) of differentiation. Details on how samples were collected and how data was generated and processed are described below.   Sample preparation NES were seeded on tissue culture flasks coated with 20 μg/ml poly-L-ornithine (Sigma-Aldrich P3655), and 1 μg/ml laminin (Sigma-Aldrich L2020). Cells were grown in DMEM/F12+GlutaMAX medium (ThermoFisher 31331093) supplemented with 0.05X B27 (ThermoFisher 17504044), 1X N2 (ThermoFisher 17502001), 10 ng/ml bFGF (fisher scientific CTP0261), 10 ng/ml EGF (PeproTech AF-100-15) and 10 U/ml penicillin/streptomycin (ThermoFisher 15140122). Medium was exchanged 50% daily and cells maintained in 5% CO2 at 37ºC, passaging once 100% confluent and seeding at a density of 5x104 cells/cm2. Neural differentiation was induced by growth factor withdrawal the day after plating with media B27 concentration increased to 0.5X. Media was exchanged 50% every second day up until D15, after which media was supplemented with 0.4 ug/ml laminin and exchanged 50% every three days.    RNA extraction and sequencing Cells were lysed in TRIzol reagent (ThermoFischer 15596026) before separating with chloroform and mixing the aqueous phase with isopropanol as per manufacturer directions. RNA was then isolated from the isopropanol/chloroform solution using the ReliaPrep RNA Cell Miniprep kit (Promega Z6010). Libraries were prepared with Illumina Truseq Stranded total RNA RiboZero GOLD kit and sequenced on the NovaSeq6000 platform with a 2x151 setup using NovaSeqXp workflow in S4 mode flowcell.   Data generation Raw reads were processed using cutadapt v3.2 to trim adaptor sequences and low-quality base pairs and discard short reads (options: -m 20 -e 0.1 -q 20 -O 1). The GRCh37 genome assembly was used for all alignment, annotation, and downstream analysis steps. Trimmed read weres alignment to the GRCh37 genome assembly using TopHat v2.0.9 tophat_fusion (with Bowtie v1.1.2 and Samtools v0.1.19) with –fusion-min-dist 200. BAM files have been anonymised by removal of potentially identifiable genetic variant information using BAMboozle v0.5.0 (Ziegenhain & Sandberg, 2021) with default settings. This BAM files and corresponding index (.bai) files are provided here with naming convention "label.bam" Information on sample labels and corresponding conditions is provided in the file 'metadata.txt'.

Exploring the utility of regulatory network-based machine learning for gene expression prediction in maize

Relevant Data and Code for Exploring the utility of regulatory network-based  machine learning for gene expression prediction in maize by Taylor Ferebee and Edward Buckler. Input Data The inputs of the models are enclosed in Input_data-2022-001.zip Output Data The outputs of the models are enclosed in Output_Results-2022-001.zip Relevant Code  The code for all analyses is enclosed in Code_Archive.zip

IFEED: Interactive Facial Expression and Emotion Detection Dataset

Interactive Facial Expression and Emotion Detection (IFEED) is an annotated dataset that can be used to train, validate, and test Deep Learning models for facial expression and emotion recognition. It contains pre-filtered and analysed images of the interactions between the six main characters of the Friends television series, obtained from the video recordings of the Multimodal EmotionLines Dataset (MELD). The images were obtained by decomposing the videos into multiple frames and extracting the facial expression of the correctly identified characters. A team composed of 14 researchers manually verified and annotated the processed data into several classes: Angry, Sad, Happy, Fearful, Disgusted, Surprised and Neutral. IFEED can be valuable for the development of intelligent facial expression recognition solutions and emotion detection software, enabling binary or multi-class classification, or even anomaly detection or clustering tasks. The images with ambiguous or very subtle facial expressions can be repurposed for adversarial learning. The dataset can be combined with additional data recordings to create more complete and extensive datasets and improve the generalization of robust deep learning models.

Growing Arabidopsis pollen tubes expressing genetically encoded reporters for calcium and pH

Spatiotemporal dynamics of intracellular pH (H+) and calcium (Ca2+) in growing Arabidopsis pollen tubes. Fluorescence time-lapses of pollen tubes expressing ratiometric sensors under the pollen-specific LAT52 promoter, namely CaMeleon (Ca2+) [Damineli et al., 2017; DOI: 10.1093/jxb/erx032] and pHluorin (pH) [Hoffmann et al., 2020; DOI: 10.1038/s41467-020-16253-1], were acquired every 4 seconds with an inverted microscope equipped with a front-illuminated camera (2560 × 2160, pixel size 6.45 μm), a fluorescence illuminator, and a ×63 1.2NA water immersion objective lens. The CaMeleon filters were set as follows: excitation 426-450 nm (CFP) and 505-515 nm (YFP), emission 458-487 nm (CFP) and 520-550 nm (YFP). As for pHluorin, the filter settings were: excitation 318-390 nm (DAPI) and 428-475 nm (FITC), emission 435-448 nm (DAPI) and 523-536 nm (FITC) [from Damineli et al., 2017; Hoffmann et al., 2020].

Pan-cancer Proteomics Analysis to Identify Tumor-Enriched and Highly Expressed Cell Surface Antigens as Potential Targets for Cancer Therapeutics

CPTAC PAN-cancer Data Repository Welcome to the CPTAC PAN-cancer Data Repository! This repository serves as a data repository for the CPTAC PAN-cancer effort, which focuses on cancer target discovery. It contains various data sets related to protein abundance estimation, derived TMT-TPA, iBAQ, iBAQ-derived copy number, and differential protein expression for CPTAC ten indications. ## Contents The repository includes the following data: - FragPipe Output: Protein abundance estimation data generated using the FragPipe software. - Derived TMT-TPA: Data derived from Tandem Mass Tag (TMT) based Total Protein Approach (TPA). - iBAQ: Data representing intensity-based absolute quantification (iBAQ) of proteins. - iBAQ-derived Copy Number: Data derived from iBAQ analysis for copy number estimation. - Differential Protein Expression: Data indicating differential expression of proteins between tumor and NAT. ## Data Organization The data in this repository is organized in a structured manner to facilitate easy access and navigation. The repository structure is as follows: FragPipe/ [fragpipe_data_files] Derived_TMT_TPA/ [derived_tmt_tpa_data_files] iBAQ/ [ibaq_data_files] iBAQ-derived_copy_number/ [ibaq_copy_number_data_files] Differential_protein_expression/ [differential_expression_data_files]

opencc-by-4.0Aug 2023View details →

Expression of a corA-lacZ transcriptional fusion in Salmonella

A corA-lacZ transcriptional fusion was shown to be activated by RpoS when Salmonella is grown to stationary phase in LB rich medium (Metaane et al.  2022)Here, expression of the corA-lacZ fusion was evaluated in Salmonella wild-type strain and rpoS mutant grown to stationary phase in LB medium containing different concentrations of Mg and in minimal medium M63 starved or not for Mg. RpoS was required fort optimal expression of the fusion in these three environmental conditions and level of expression was slightly higher when the extracellular magnesium concentration was low.Metaane S, Monteil V, Ayrault S, Bordier L, Levi-Meyreuis C, Norel F. The stress sigma factor sigmaS/RpoS counteracts Fur repression of genes involved in iron and manganese metabolism and modulates the ionome of Salmonella enterica serovar Typhimurium. PloS one 2022, 17(3):e0265511.This work was supported by the French National Research Agency (ANR-19-CE44-0005-01, PERIOMET project).See also:Metaane S, Monteil V, Douché T, Giai Gianetto Q, Matondo M, Maufrais C, Norel F. Loss of CorA, the primary magnesium transporter of Salmonella, is alleviated by MgtA and PhoP-dependent compensatory mechanisms. PloS one 2023, 18(9):e0291736.NOREL, MONTEIL, & METAANE. (2023). Towards new elements involved in magnesium and cobalt trafficking in Salmonella serovar Typhimurium. Zenodo. <a href="https://doi.org/10.5281/zenodo.8086417">https://doi.org/10.5281/zenodo.8086417</a>NOREL, METAANE, & MONTEIL. (2023). Detection of physical interactions between the magnesium transporter CorA and other Cor proteins using the bacterial two hybrid system (BACTH). Zenodo. <a href="https://doi.org/10.5281/zenodo.7994619">https://doi.org/10.5281/zenodo.7994619</a>NOREL Francoise, MONTEIL Veronique, DOUCHE Thibaut, & MATONDO Mariette. (2023). Global effects of deletions of the sitABCD, mntH, cbiMNQO and corA genes, encoding transporters for manganese, cobalt and magnesium on protein abundance in Salmonella enterica serovar Typhimurium grown to stationary phase in LB. [Data set]. Zenodo. <a href="https://doi.org/10.5281/zenodo.8279780">https://doi.org/10.5281/zenodo.8279780</a>

opencc-by-4.0Dec 2023View details →

Expression of mgtA encoding a magnesium transporter is activated in the absence of the main Mg2+ transporter CorA in Salmonella

Salmonella imports magnesium via three known transporters, the widely conserved CorA transporter and the MgtA and MgtB P-type ATPases. CorA is expressed under various growth conditions whereas the other two magnesium transporters, MgtA and MgtB, are expressed under conditions of magnesium starvation under the positive control of the PhoP-PhoQ regulatory system.                         Our recent results suggest that production of MgtA, but not that of MgtB, is activated in the absence of the main Mg2+ transporter CorA (Metaane et al 2022, 2023 )                         This hypothesis was further validated in this study by using transcriptional and translational lacZ fusions in the mgtA and mgtB genes. In addition, our data suggest that regulation of expression of MgtA in the absence of CorA is post-transcriptional .   This work was supported by the French National Research Agency (ANR-19-CE44-0005-01, PERIOMET project).     Metaane S, Monteil V, Ayrault S, Bordier L, Levi-Meyreuis C, Norel F. The stress sigma factor sigmaS/RpoS counteracts Fur repression of genes involved in iron and manganese metabolism and modulates the ionome of Salmonella enterica serovar Typhimurium. PLoS One 2022;17(3):e0265511.Metaane S, Monteil V, Douché T, Giai Gianetto Q, Matondo M, Maufrais C, Norel F. Loss of CorA, the primary magnesium transporter of Salmonella, is alleviated by MgtA and PhoP-dependent compensatory mechanisms. PLoS One 2023;18(9):e0291736.

opencc-by-4.0Jun 2023View details →

N6-Methyladenosine Directly Regulates CD40L Expression In CD4+ T Lymphocytes

Abstract T cell activation is a highly regulated process, modulated via the expression of various immune regulatory proteins including cytokines, surface receptors and co-stimulatory proteins. N6-methyladenosine (m6A) is an RNA modification that can directly regulate RNA expression levels and it is associated with various biological processes. However, the function of m6A in T cell activation remains incompletely understood. We identify m6A as a novel regulator of the expression of CD40 ligand (CD40L) in human CD4+ lymphocytes. Manipulation of the m6A ‘eraser’ fat mass and obesity-associated protein (FTO) and m6A ‘writer’ protein methyltransferase-like 3 (METTL3) directly affects the expression of CD40L. The m6A ‘reader’ protein YT521-B homology domain family-2 (YTHDF2) is able to recognize and bind m6A specific sequences on the CD40L mRNA and promotes its degradation. This study demonstrates that CD40L expression in human primary CD4+ T lymphocytes is regulated via m6A modifications, elucidating a new regulatory mechanism in CD4+ T cell activation that could possibly be leveraged in the future to modulate T cell responses in patients with immune-related diseases.   Data deposited <ul> <li>meRIP sequencing: read counts of healthy control peripheral blood-derived CD4+ T lymphocytes (figure 1 in article).</li> <li>meRIP sequencing: per gene TMM normalized log2(CPM + 0.168) expression values of healthy control peripheral blood-derived CD4+ T lymphocytes (figure 1 in article). Also includes Log2FoldChange values or each gene.</li> </ul>

opencc-by-4.0Feb 2022View details →

Spatio-temporal, optogenetic control of gene expression in organoids

Organoids derived from stem cells become increasingly important to study human development and to model disease. However, methods are needed to control and study spatio-temporal patterns of gene expression in organoids. To this aim, we combined optogenetics and gene perturbation technologies to activate or knock-down RNA of target genes, at single-cell resolution and in programmable spatio-temporal patterns. To illustrate the usefulness of our approach, we locally activated Sonic Hedgehog (SHH) signaling in an organoid model for human neurodevelopment. High-resolution spatial transcriptomic and single-cell analyses showed that this local induction was sufficient to generate stereotypically patterned organoids in three dimensions and revealed new insights into SHH’s contribution to gene regulation in neurodevelopment. With this study, we propose optogenetic perturbations in combination with spatial transcriptomics as a powerful technology to reprogram and study cell fates and tissue patterning in organoids.

opencc-by-4.0Jan 2023View details →

Gene expression dataset of the Spatially Resolved Single-cell Translatomics at Molecular Resolution

Here are the gene expression datasets of RIBOmap included in "Spatially Resolved Single-cell Translatomics at Molecular Resolution" from Zeng et al. Please refer to the README file for more detailed information.    Abstract The precise control of mRNA translation is a crucial step in post-transcriptional gene regulation of cellular physiology. However, it remains a major challenge to systematically study mRNA translation at the transcriptomic scale with spatial and single-cell resolution. Here, we report the development of RIBOmap, a three-dimensional (3D) in situ profiling method to detect mRNA translation of thousands of genes simultaneously in intact cells and tissues. By applying RIBOmap to 981 genes in HeLa cells, we revealed a remarkable dependency of translation on cell-cycle stages and subcellular localization. Furthermore, we profiled single-cell translatomes of 5,413 genes in adult mouse brain tissues yielding a spatial cell atlas of 119,173 cells. The pairwise spatial mapping of single-cell translatome and transcriptome in two adjacent mouse brain slices revealed cell-type and brain-region-dependent translational regulation and suggested a translation remodeling during oligodendrocyte lineage maturation. The spatial translatome profiling detected widespread patterns of localized translation in neuronal and glial cells in intact brain tissue networks. Together, RIBOmap presents the first spatially resolved single-cell translatomics technology, accelerating our understanding of protein synthesis in the context of subcellular architecture, cell types, and tissue anatomy.

opencc-zeroJun 2023View details →

Trans-acting genotypes drive mRNA expression affecting metabolic and thermal tolerance traits

Evolutionary processes driving physiological trait variation depend on the underlying genomic mechanisms. Evolution of these mechanisms depends on whether traits are genetically complex (involving many genes) and how gene expression that impacts the traits is converted to phenotype. Yet, genomic mechanisms that impact physiological traits are diverse and context-dependent (e.g., vary by environment or among tissues), making them difficult to discern. Here we examine the relationships between genotype, mRNA expression, and physiological traits to discern the genetic complexity and whether the gene expression affecting the physiological traits is primarily cis or trans-acting. We use low-coverage whole genome sequencing and tissue-specific mRNA expression among individuals to identify polymorphisms directly associated with physiological traits and expressed quantitative trait loci (eQTL) driving variation in six temperature-specific physiological traits (standard metabolic rate, thermal tolerance, and four substrate-specific cardiac metabolic rates). Not surprisingly, there were few, only five, SNPs directly associated with physiological traits. Yet, by focusing on a select set of mRNAs belonging to co-expression modules that explain up to 82% of temperature specific (12°C or 28°C) metabolism and thermal tolerance, we identified hundreds of significant eQTL for mRNA whose expression affects physiological traits. Surprisingly, most eQTL (97.4% for heart and 96.7% for brain) of eQTL were trans-acting. This could be due to higher effect size or greater importance of trans versus cis-acting eQTLs for mRNAs that are central to co-expression modules. That is, we may have enhanced the identification of trans-acting factors by looking for SNPs associated with mRNAs in co-expression modules that are known to be correlated with the expression of 10s or 100s of other genes, and thus have identified eQTLs with widespread effects on broad gene expression patterns. Overall, these data indicate that the genomic mechanism driving physiological variation across environments is driven by trans-acting tissue-specific mRNA expression.

opencc-zeroJun 2023View details →

Decreased FAM13B expression increases atrial fibrillation susceptibility by regulating sodium current and calcium handling

Objectives: To determine the causal genetic variant and gene and the mechanism for the atrial fibrillation (AF) genome wide association study (GWAS) locus on chromosome 5q31. Background: FAM13B expression is strongly associated with the lead AF GWAS variant at 5q31. However, the regulatory variant controlling FAM13B expression and the mechanism by which FAM13B impacts AF susceptibility are not known. Methods: Bioinformatics, reporter gene transfections, gel shifts, and gene editing were used to identify the variant regulating FAM13B expression. RNAseq after FAM13B knockdown in stem cell-derived cardiomyocytes (iCMs) identified downstream processes. Patch clamp and calcium transient assays were used to assess downstream mechanisms. Fam13b knockout (KO) mice were studied for heart structural and functional changes, and pacing-induced arrhythmia. Results: rs17171731 was identified as the regulatory variant controlling FAM13B expression, with decreased enhancer activity of the risk allele. Knockdown of FAM13B in iCMs altered expression of >1000 genes including SCN2B and led to pro-arrhythmogenic changes in the late sodium current and Ca2+ cycling. FAM13B is a member of the Rho GTPase-activating protein (RhoGAP) gene family, but failed to demonstrate RhoGAP activity. GFP-tagged FAM13B expressed in iCMs localized at the Z-disc and plasma membrane. Fam13b knockout mice had increased basal p-wave duration and QT interval, and were more susceptible to pacing-induced arrhythmias vs. controls. Conclusions: This study went from an AF GWAS locus to identify the causal variant and gene, mechanisms for this association, and confirmed arrhythmia susceptibility in Fam13b KO mice. FAM13B and downstream effectors are potential targets for patient-specific therapeutics.

opencc-by-4.0Jul 2023View details →

Heterogeneous Receptor Expression Underlies Non-uniform Peptidergic Modulation of Olfaction in Drosophila

Original confocal scans for all light microscopy images in the main and supplementary figures of Sizemore et al., 2023.  If you make use of this data, please cite: Heterogeneous Receptor Expression Underlies Non-uniform Peptidergic Modulation of Olfaction in Drosophila Tyler R. Sizemore, Julius Jonaitis, Andrew M. Dacks doi: 10.1038/s41467-023-41012-3