The EXPANDER Integrated Platform for Transcriptome Analysis

Hait, Tom Aharon; Maron‐Katz, Adi; Sagir, Dorit; Amar, David; Ulitsky, Igor; Linhart, Chaim; Tanay, Amos; Sharan, Roded; Shiloh, Yosef; Elkon, Ran; Shamir, Ron

doi:10.1016/j.jmb.2019.05.013

Cited by 30 publications

(20 citation statements)

References 36 publications

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“…Based on the FPKM expression of genes and lncRNAs, the K ‐means ( K = 8) method was used for cluster analysis by Expander (Hait et al, 2019). Heatmaps were based on the default hierarchical clustering method in R and figures were produced using the package pheatmap (https://cran.r-project.org/package=pheatmap).…”

Section: Methodsmentioning

confidence: 99%

Long non‐coding RNAs associate with jasmonate‐mediated plant defence against herbivores

Jin

et al. 2020

Plant Cell & Environment

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Long non‐coding RNA (lncRNA) are important regulators of many biological processes in plants, including defence against pathogens; whether lncRNAs mediate defence against herbivore attack is yet to be explored. With wild tobacco, Nicotiana attenuata, and its well‐characterized interactions with herbivores, we identified a total of 1,290 significantly up‐ or down‐regulated lncRNAs in response to a precise herbivore elicitation treatment. Of these, long intergenic non‐coding RNAs (lincRNAs) were the most abundant. Based on their expression patterns, these up‐regulated lincRNAs were classified as early (<1 hr) or late (>3 hr) responders. The early responding lincRNAs had accumulation patterns that tracked the herbivore‐elicited burst of bioactive jasmonates (JAs) and the expression of regulator genes in JA signalling which regulate plant defences against herbivores. Silencing two of these early responders in N. attenuata (JAL1 and JAL3) significantly attenuated the accumulation of JAs, JA‐mediated defensives and the plant's resistance to M. sexta attack, suggesting roles in regulating JA‐mediated plant defence. By lincRNA sequencing of JA‐deficient lines, many late responder lincRNAs were found to be transcriptionally regulated by JA signalling. This study uncovers a new role of lncRNAs in JA‐mediated herbivore resistance.

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Section: Methodsmentioning

confidence: 99%

Long non‐coding RNAs associate with jasmonate‐mediated plant defence against herbivores

Jin

et al. 2020

Plant Cell & Environment

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“…Cluster analysis was applied to the union of the DEGs detected in either the OHC or SC dataset. It was done using the CLuster Identification via Connectivity Kernels (CLICK) algorithm (with default parameters) implemented in the EXpression Analyzer and DisplayER (EXPANDER) package (Hait et al, 2019). In the combined analysis of the OHC and SC datasets, two additional Prestin-CreER T2 ;RiboTag;CBA/CaJ samples (1 input and 1 IP at 6h) were excluded as they appeared as outlier in the principal component analysis.…”

Section: Ribotag Datasetsmentioning

confidence: 99%

A cell-type-specific atlas of the inner ear transcriptional response to acoustic trauma

Milon

Shulman

et al. 2021

Cell Reports

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“…We ranked the LFCs from highest to lowest, and applied the gene set enrichment analysis (GSEA) 21 implemented in Expander 22 . We chose to apply 1000 permutation tests.…”

Section: Analysis Of Lymphoblastoid Rna-seq Datamentioning

confidence: 99%

Tauopathy in the young autistic brain: novel biomarker and therapeutic target

et al. 2020

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Given our recent discovery of somatic mutations in autism spectrum disorder (ASD)/intellectual disability (ID) genes in postmortem aged Alzheimer's disease brains correlating with increasing tauopathy, it is important to decipher if tauopathy is underlying brain imaging results of atrophy in ASD/ID children. We concentrated on activity-dependent neuroprotective protein (ADNP), a prevalent autism gene. The unique availability of multiple postmortem brain sections of a 7-year-old male, heterozygous for ADNP de novo mutation c.2244Adup/p.His559Glnfs*3 allowed exploration of tauopathy, reflecting on a general unexplored mechanism. The tested subject exhibited autism, fine motor delays, severe intellectual disability and seizures. The patient died after multiple organ failure following liver transplantation. To compare to other ADNP syndrome mutations, immortalized lymphoblastoid cell lines from three different patients (including ADNP p.Arg216*, p.Lys408Valfs*31, and p.Tyr719* heterozygous dominant mutations) and a control were subjected to RNA-seq. Immunohistochemistry, high-throughput gene expression profiles in numerous postmortem tissues followed. Comparisons to a control brain and to extensive datasets were used. Live cell imaging investigated Tau-microtubule interaction, protecting against tauopathy. Extensive child brain tauopathy paralleled by multiple gene expression changes was discovered. Tauopathy was explained by direct mutation effects on Tau-microtubule interaction and correction by the ADNP active snippet NAP. Significant pathway changes (empirical P value < 0.05) included over 100 genes encompassing neuroactive ligand-receptor and cytokine-cytokine receptor interaction, MAPK and calcium signaling, axon guidance and Wnt signaling pathways. Changes were also seen in steroid biosynthesis genes, suggesting sex differences. Selecting the most affected genes by the ADNP mutations for gene expression analysis, in multiple postmortem tissues, identified Tau (MAPT)-gene-related expression changes compared with extensive normal gene expression (RNA-seq) databases. ADNP showed relatively reduced expression in the ADNP syndrome cerebellum, which was also observed for 25 additional genes (representing >50% of the tested genes), including NLGN1, NLGN2, PAX6, SMARCA4, and SNAP25, converging on nervous system development and tauopathy. NAP provided protection against mutated ADNP disrupted Tau-microtubule association. In conclusion, tauopathy may explain brain-imaging findings in ADNP syndrome children and may provide a new direction for the development of tauopathy protecting drug candidates like NAP in ASD/ID.

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The EXPANDER Integrated Platform for Transcriptome Analysis

Cited by 30 publications

References 36 publications

Long non‐coding RNAs associate with jasmonate‐mediated plant defence against herbivores

Long non‐coding RNAs associate with jasmonate‐mediated plant defence against herbivores

A cell-type-specific atlas of the inner ear transcriptional response to acoustic trauma

Tauopathy in the young autistic brain: novel biomarker and therapeutic target

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