Journal: Nature Communications

Article Title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia

doi: 10.1038/s41467-018-06515-4

Figure Lengend Snippet: Summary schematic of experimental and analytic pipeline. a One hundred and thirty-five drugs were prioritized for screening based on connectivity with diverse aspects of SZ-related biology. b Cells used for screening comprised seven CCLs (A549, AGS, A673, HEPG2, HT29, MCF7, and VCAP) that were prioritized using LINCs datasets, one additional neural CCL (SH-SY5Y) and hiPSC NPCs from 13 SZ and 13 control individuals (12 each per drug). c Data were generated using the L1000 platform to yield 6650 drug-perturbation transcriptomic profiles (135 drugs tested across 26 hiPSC NPCs and 8 CCLs). After data quality control, normalized expression was converted to d robust Z -scores based on comparison with isogenic DMSO-treated experiments, and used as inputs for e functional molecular enrichments, cell-type-specific (hiPSC NPCs and CCLs) trends, diagnosis-dependent (SZ and control) responses, and chemogenomics analyses. Global transcriptomic responses of two drugs were tested across hiPSC NPCs from three SZ and three control individuals by RNA-seq, as part of a validation of the L1000 results

Article Snippet: The L1000 gene-expression profiling assay (Genometry, Inc.) was used to generate data; GCT files with intra-sample scaled, intra-batch quantile-normalized, and log2-transformed data were received and used for downstream analysis.

Techniques: Control, Generated, Expressing, Comparison, Functional Assay, Biomarker Discovery, RNA Sequencing

Journal: Nature Communications

Article Title: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia

doi: 10.1038/s41467-018-06515-4

Figure Lengend Snippet: Loxapine-induced regulation of FMRP targets implicates NPD-associated binding motifs. a Summary of diagnosis-dependent drug-induced perturbations in FMR1 protein (FMRP) targets from L1000 drug-screening data. Red (upregulation) and blue (downregulation) points indicate drugs that induce significant (FDR < 0.1) changes in the regulation of FMRP targets in SZ hiPSC NPCs in two FMRP target sets , . b SZ sets that are most differentially regulated by methylparaben and loxapine, across L1000 and RNA-seq. Squares with enrichment FDR > 0.1 are shown as white. c Known FMRP-binding motifs in DE genes of loxapine-treated SZ and control hiPSC NPCs. d FMRP targets enriched in loxapine-treated diagnosis-dependent hiPSC NPC DE genes were tested for association with SZ, ASD, and intellectual disability (ID) rare variant gene lists. e Enrichment for ACUK FMRP-binding motif variants identified in NPD mutations. f Enrichment for ACUK FMRP-binding motif variants identified in neuropsychiatric disease mutations with essential splice sites

Article Snippet: The L1000 gene-expression profiling assay (Genometry, Inc.) was used to generate data; GCT files with intra-sample scaled, intra-batch quantile-normalized, and log2-transformed data were received and used for downstream analysis.

Techniques: Binding Assay, Biomarker Discovery, Drug discovery, RNA Sequencing, Control, Variant Assay

Journal: Journal for Immunotherapy of Cancer

Article Title: HDAC9 deficiency promotes tumor progression by decreasing the CD8 + dendritic cell infiltration of the tumor microenvironment

doi: 10.1136/jitc-2020-000529

Figure Lengend Snippet: Transcriptome-wide changes in histone deacetylase 9 (HDAC9)-deficient bone marrow–derived dendritic cells (BMDCs). (A) Volcano plots of differentially expressed genes (DEGs) in wild-type (WT) and Hdac9 -/- BMDCs (adjusted p≤0.05, fold change ≥2.0). Statistical significance was determined by two-sided likelihood ratio test (n=4). (B) Gene ontology term enrichment analysis of biological process-associated genes with significantly differential translational efficiency (p≤0.00053 and fold enrichment ≥5.2). (C) Heatmap showing the translational efficiency of genes involved in immune system processes in WT and Hdac9 -/- BMDCs (KO1 and KO2 represent replicates). FDR, false discovery rate; KO, knockout.

Article Snippet: RNA quality was determined and high-quality samples (optical density (OD) 260/280=1.8–2.2, OD 260/230≥2.0, RNA integrity number ≥6.5, 28S:18S ≥1.0, >10 μg) were used to construct RNA-seq transcriptome libraries with the TruSeq RNA Sample Preparation Kit (Illumina; San Diego, California, USA), using 1 μg of total RNA.

Techniques: Histone Deacetylase Assay, Derivative Assay, Knock-Out

Journal: Frontiers in Pharmacology

Article Title: VASN knockout induces myocardial fibrosis in mice by downregulating non-collagen fibers and promoting inflammation

doi: 10.3389/fphar.2024.1500617

Figure Lengend Snippet: Transcriptome analysis of MF in VASN-deficient mice. The present study entailed heart tissues from VASN +/+ (n = 3), VASN +/− (n = 3), and VASN −/− (n = 3) mice for transcriptome sequencing. (A) Differentially expressed genes (DEGs) based on miRNA transcriptome data; (B) volcano plot presenting the key genes involved in differential expression; (C) KEGG enrichment plot of all DEGs in WT-HO; (D) GO enrichment map of all DEGs in WT-HO; (E) WT-HO differential gene heatmap and KEGG annotation; (F) interaction diagram of the top-8 entries in KEGG for all DEGs in WT-HO; (G) extracellular matrix pathway gene protein interaction network diagram.

Article Snippet: Transcriptome sequencing of the hearts from the three groups was performed at the Wuhan Genome Institute (BGI-Shenzhen), where a total of 12 RNA samples (three mice per group) were sequenced.

Techniques: Sequencing, Quantitative Proteomics

Journal: Mutagenesis

Article Title: Towards an advanced testing strategy for genotoxicity using image-based 2D and 3D HepG2 DNA damage response fluorescent protein reporters

doi: 10.1093/mutage/geab031

Figure Lengend Snippet: Hepatocyte maturation status of four different HepG2 models. (A) Bright field pictures showing morphological differences between the different models; HepG2 cultured in 2D and normal DMEM medium, HepG2 cultured in 2D and AAGLY medium, HepG2 cultured in 3D and normal DMEM medium, HepG2 cultured in 3D and AAGLY medium from left to right. (B) Gene expression profiles of some hepatocyte markers ( SERPINA1 and ALB ), CYP enzymes ( 3A4 , 3A7 and 1B1 ) and transporters ( UGT1A1 and SLC10A1 ) and the housekeeping genes ( GAPDH ). Gene expression values are relative to model 1 (HepG2 cultured in 2D and normal DMEM medium) and benchmarked to a pool of 10 different donors of cryopreserved PHHs (10×). N = 6; error bars represent SD; significance levels represented as * P adj < 0.05, ** P adj < 0.01 and *** P adj < 0.001.

Article Snippet: Samples were lysed for 15 min at room temperature, stored at −80°C and shipped for transcriptome analysis by BioSpyder.

Techniques: Cell Culture, Gene Expression

Journal: Data in Brief

Article Title: Data on microRNAs and microRNA-targeted mRNAs in Xenopus ectoderm

doi: 10.1016/j.dib.2016.09.054

Figure Lengend Snippet:

Article Snippet: The reference index was prepared from Xenopus laevis transcriptome dataset (courtesy of Taejoon Kwan and Ed Marcotte, UT Austin).

Techniques: Next-Generation Sequencing, Generated, Sequencing