Journal: iScience

Article Title: Profiling of diverse tumor types establishes the broad utility of VHL-based ProTaCs and triages candidate ubiquitin ligases

doi: 10.1016/j.isci.2022.103985

Figure Lengend Snippet: Correlation of PROTAC activity with CRBN and VHL RNA expression, DNA copy number, and protein level (A and B) DC50 values from the cell line panel for each compound were used to group the cell lines into the bottom (low) and top (high) quartiles. Low and high quartiles were plotted against ligase mRNA expression or copy number, p values from unpaired two-samples, two-sided Wilcoxon rank sum tests of the groups were calculated. (A) dBET1 activity correlates significantly with CRBN copy number, p = 0.00058, and mRNA expression, p = 0.0048. Cell lines with non-synonymous mutations of CRBN were marked in red. (B) MZ1 activity correlates with VHL RNA expression, p = 0.028 but not VHL copy number, p = 0.059. Cell lines with non-synonymous mutations of VHL were marked in red. (C) Dose-response curves from representative kidney-derived cancer cell lines are shown; 786-O is devoid of both VHL and CRBN activity, 769P is lacking VHL activity. Dose titration curves are derived from n = 2 independent experiments, error bars represent standard error of the mean (SEM). (D) Lysates from untreated cells were separated by capillary electrophoresis, VHL and CRBN proteins were immune-detected. Each of the five kidney-derived cancer cell lines is lacking VHL protein, all of the cell lines express appreciable CRBN protein. (E) Dose-response curves from two representative lung cancer cell lines, H23 lacks dBET1-CRBN-associated activity. Dose titration curves are derived from n = 2 independent experiments, error bars represent standard error of the mean (SEM). (F) Lung-derived cancer cell lines with low CRBN activity have low or no CRBN protein, all lung cancer cell lines express VHL protein.

Article Snippet: For this analysis, we retrieved RNA-Seq expression and DNA alteration data from available OmicSoft TCGA data sets and graphed these by TCGA-designated tumor type ( B).

Techniques: Activity Assay, RNA Expression, Expressing, Derivative Assay, Titration, Electrophoresis

Journal: iScience

Article Title: Profiling of diverse tumor types establishes the broad utility of VHL-based ProTaCs and triages candidate ubiquitin ligases

doi: 10.1016/j.isci.2022.103985

Figure Lengend Snippet: Comparison of genomic features for seven PROTAC Ub-ligases (A) Boxplot showing the distribution of log transformed fold change of the expression of seven Ub-ligases in cancer tissue compared to its paired non-cancer control tissue. Only cancer types with at least 50 non-cancer control tissue samples were included. (B) DNA alternation landscape of seven Ub-ligases across cancer types in TCGA. Bar graph showing percentage of samples harboring each Ub-ligase mutations across tumor types, the number of samples altered are labeled in the right side of each bar. Different mutation types are color labeled, with red representing amplification, blue representing homozygous deletion, green representing non-synonymous mutations, and gray representing a mixture of the above type of mutations. (C) Genome-scale CRISPR-Cas9 essentiality screen results for genes in across different cancer cell lines performed by the Broad Institute were characterized by dependency score (CERES) to reflect the functional importance of genes in certain cancer types. Boxplots summarized the distribution of CERES score of each ligase receptor in cell lines of representative tumor types. A lower score means that a gene is more likely to be essential for the cancer cell line survival and proliferation. A score of −1 corresponds to the median of all common essential genes, used as a cutoff indicator here.

Article Snippet: For this analysis, we retrieved RNA-Seq expression and DNA alteration data from available OmicSoft TCGA data sets and graphed these by TCGA-designated tumor type ( B).

Techniques: Comparison, Transformation Assay, Expressing, Control, Labeling, Mutagenesis, Amplification, CRISPR, Functional Assay

Journal: Database: The Journal of Biological Databases and Curation

Article Title: TISSUES 2.0: an integrative web resource on mammalian tissue expression

doi: 10.1093/database/bay003

Figure Lengend Snippet: In order to obtain confidence scores for each gene–tissue pair, we assess the relationship between raw expression values and fold enrichment, defined as the agreement between each dataset and gold standard datasets specific to the organism. The gold standard datasets are based on the UniProtKB protein tissue annotations in human, filtered for 1-to-1 orthologs between human and each of the three organisms. The x -axis contains raw expression values for gene–tissue pairs, in units specific to the type of experiment or processing of data (e.g. intensity units for microarray studies, FPKMs for RNA-seq), and averaged across bins of 100 pairs.

Article Snippet: The dataset produced at the Wageningen University under the FAANG project (Functional Annotation of Animal Genomes) consists of RNA sequencing data for eight porcine tissues and three different breeds (duroc, large white, pietrain).

Techniques: Expressing, Microarray, RNA Sequencing

Journal: iScience

Article Title: Tissue-resident memory T cell signatures from single-cell analysis associated with better melanoma prognosis

doi: 10.1016/j.isci.2024.109277

Figure Lengend Snippet:

Article Snippet: RNA-seq data and clinical information for TCGA-SKCM , Broad Institute , TCGA ( https://gdac.broadinstitute.org/ ).

Techniques: Mutagenesis, Biomarker Discovery, Software