Journal: Discover Oncology

Article Title: Genetic evidence supporting obesity as a risk factor for lung squamous cell carcinoma and the identification of MFAP1 as a shared genetic target

doi: 10.1007/s12672-026-04793-9

Figure Lengend Snippet: Flowchart Overview of this MR-based study. LD linkage disequilibrium, ρ-HESS Heritability Estimation from Summary Statistics, GNOVA Genetic covariance analyser, MTAG Multi-Trait Analysis of GWAS, CPASSOC Cross Phenotype Association, GWAS Genome-wide Association Study, MR Mendelian Randomization, GSMR Generalized summary-data-based Mendelian randomization, LDSC-SEG linkage disequilibrium score regression applied to specifically expressed genes, MAGMA Multi-marker Analysis of GenoMic Annotation, SMR Summary-databased Mendelian randomization, Phe-MR phenotypes, MR BMI body mass index, LUSC squamous cell lung cancer; scRNA-seq single-cell RNA sequencing

Article Snippet: The Single-cell RNA sequencing gene expression data were available from https://www.ncbi.nlm.nih.gov/geo/ and [https://singlecell.broadinstitute.org/single_cell](https:/www.singlecell.broadinstitute.org/single_cell) .

Techniques: GWAS, Marker, Single Cell, RNA Sequencing

Journal: Discover Oncology

Article Title: Genetic evidence supporting obesity as a risk factor for lung squamous cell carcinoma and the identification of MFAP1 as a shared genetic target

doi: 10.1007/s12672-026-04793-9

Figure Lengend Snippet: Tissue- and cell type–specific enrichment of SNP heritability for BMI and LUSC. A Tissue-level SNP heritability enrichment for BMI across 53 GTEx tissues estimated using LDSC-SEG. The x-axis shows tissues grouped by organ system, and the y-axis shows the estimated enrichment coefficient (log-scaled or standardized). Tissues surpassing the significance threshold (FDR-adjusted P < 0.05) are highlighted. B Tissue-level SNP heritability enrichment for LUSC using the same LDSC-SEG framework. The x-axis indicates GTEx tissues and the y-axis indicates enrichment coefficients, as in panel ( A ). Tissues with significant enrichment (FDR-adjusted P < 0.05) are labelled, illustrating the overlap and differences in tissue-specific genetic architecture between BMI and LUSC. C – G Cell type–specific SNP heritability enrichment for BMI and LUSC across single-cell RNA sequencing datasets from brain, ileum, heart, and colon, estimated using MAGMA-based cell typing. For each tissue, the left panel shows enrichment for BMI and the right panel shows enrichment for LUSC. The y-axis lists cell types (for example, neurons, epithelial cells, eosinophils, CD8⁺ T cells), and the x-axis shows –log₁₀(P) values for the association between cell type–specific expression and SNP heritability. Cell types with P < 0.05 are indicated in red, highlighting those most strongly enriched for the genetic signal of BMI and/or LUSC. BMI body mass index, LUSC lung squamous cell carcinoma, SNP single nucleotide polymorphism, LDSC-SEG linkage disequilibrium score regression applied to specifically expressed genes, MAGMA Multi-marker Analysis of GenoMic Annotation, scRNA-seq single-cell RNA sequencing, GTEx Genotype-Tissue Expression

Article Snippet: The Single-cell RNA sequencing gene expression data were available from https://www.ncbi.nlm.nih.gov/geo/ and [https://singlecell.broadinstitute.org/single_cell](https:/www.singlecell.broadinstitute.org/single_cell) .

Techniques: Single Cell, RNA Sequencing, Expressing, Marker

Journal: bioRxiv

Article Title: An abundance of brain-expressed genes show ectopic activation in lung adenocarcinoma

doi: 10.1101/2023.09.12.557389

Figure Lengend Snippet: A) Workflow of the analysis of RNA -seq data for the selection of genes ectopically activated in LUAD cells (EctopEx genes). B) EctopEx gene expression in a panel of normal tissues available from GTE x was clustered using Ward’s method and Euclidean distance. Expression data are depicted in log2 transformed median TPM + 1.

Article Snippet: Normalized single cell RNA -seq expression data were downloaded from the Human Protein Atlas (HPA) v20.1 ( ).

Techniques: RNA Sequencing, Selection, Gene Expression, Expressing, Transformation Assay

Journal: bioRxiv

Article Title: An abundance of brain-expressed genes show ectopic activation in lung adenocarcinoma

doi: 10.1101/2023.09.12.557389

Figure Lengend Snippet: A) Lists of LUAD Ectopex genes in the CB or CBT category were defined according to their tissue-specificity of expression ( GTE x RNA -seq). B) CBT transcripts were analysed with the Integrative Genomics Viewer ( IGV ) to define transcriptional start sites (TSS) usage in LUAD cell lines, brain cortex, and testis. The table depicts the different cases of TSS usage. Left: schematic representation of possible CBT promoter usage (broken arrows depicting TSS). Middle: screenshot of IGV views of representative CBT transcripts (black boxes: exons; connecting lines: introns; and splice junctions of RNA -seq reads represented in red or blue according to the orientation of the gene on the chromosome). Right: number of CBT genes with corresponding promoter usage.

Article Snippet: Normalized single cell RNA -seq expression data were downloaded from the Human Protein Atlas (HPA) v20.1 ( ).

Techniques: Expressing, RNA Sequencing

Journal: bioRxiv

Article Title: An abundance of brain-expressed genes show ectopic activation in lung adenocarcinoma

doi: 10.1101/2023.09.12.557389

Figure Lengend Snippet: A) Single-cell RNA -seq data of brain tissue available from HPA were explored to determine cell type-specificity of CB and CBT genes. Gene expression was clustered using Ward’s method and Euclidean distance in the available cell types of the brain. Data are depicted using a z-score of protein coding transcripts per million. B) Results of enrichment analysis of CB and CBT genes using “biological process” subcategories of Gene Ontology annotation. Top 10 enrichment scores are depicted (p-adjusted <0.05).

Article Snippet: Normalized single cell RNA -seq expression data were downloaded from the Human Protein Atlas (HPA) v20.1 ( ).

Techniques: RNA Sequencing, Gene Expression

Journal: bioRxiv

Article Title: An abundance of brain-expressed genes show ectopic activation in lung adenocarcinoma

doi: 10.1101/2023.09.12.557389

Figure Lengend Snippet: A) Heatmap depicting m RNA expression levels (log2 TPM +1) of CB and CBT genes in LUAD tissues and normal matching tissues ( TCGA ). Unsupervised hierarchical clustering was applied to LUAD samples. B) Activation frequencies ( TPM ≥2) and mean expression levels of CB, CBT and CT genes in LUAD samples were computed. C) Immunohistochemical data for CB / CBT proteins that were available at the HPA are presented. HPA scored these proteins positive in normal brain and LUAD , but negative in normal lung. D) Observed numbers of CB, CBT and CT genes with ectopic expression in LUAD were compared to their expected numbers, which were inferred from their proportions among the genes initially identified as not being expressed in normal lung and AT2 cells. (Chi-squared test, ***: p-value < 0.001, *: p-value < 0.05).

Article Snippet: Normalized single cell RNA -seq expression data were downloaded from the Human Protein Atlas (HPA) v20.1 ( ).

Techniques: RNA Expression, Activation Assay, Expressing, Immunohistochemical staining

Journal: bioRxiv

Article Title: An abundance of brain-expressed genes show ectopic activation in lung adenocarcinoma

doi: 10.1101/2023.09.12.557389

Figure Lengend Snippet: A) List of CB and CBT genes showing binding of the REST repressor (ChIP-seq) according to the i- cis Target webtool. B) RNA -seq data (normalized counts) of adult dermal fibroblasts transfected with either control (sh-ctrl) or REST -targeting sh RNA s (sh- REST ) were analyzed. Expression levels of CB / CBT genes displaying significant induction upon REST depletion ( p -value < 0.05) are depicted. The data of three CT genes (not expected to be regulated by REST ) are shown for comparison. C) m RNA levels of CB / CBT genes were compared in REST low (n=78) and REST high (n=1204) tumor cell lines of various origins (excluding the nervous system). Boxplots (Whiskers, 5-95 percentile) of select CB / CBT genes are depicted, together with that of MAGEA1 used as a REST -independent control gene. P values were calculated (Mann Whitney tests).

Article Snippet: Normalized single cell RNA -seq expression data were downloaded from the Human Protein Atlas (HPA) v20.1 ( ).

Techniques: Binding Assay, ChIP-sequencing, RNA Sequencing, Transfection, Control, Expressing, Comparison, MANN-WHITNEY