Comparative Transcriptome Analysis to Reveal Differentially Expressed Cytochrome P450 in Response to Imidacloprid in the Aphid Lion, Chrysoperla zastrowi sillemi (Esben-Petersen).

Squamous Cell Carcinoma Arising From Keratoacanthoma: An Evaluation by RT-PCR.

Normal adult liver is uniquely capable of renewal and repair after injury. Whether this response represents simple hyperplasia of various liver elements or requires recapitulation of the genetic program of the developing liver is not known. To study these possibilities, we examined transcriptional programs of adult liver after partial hepatectomy and contrasted these with developing embryonic liver. Principal component analysis demonstrated that the time series of gene expression during liver regeneration does not segregate according to developmental transcription patterns. Gene ontology analysis revealed that liver restoration after hepatectomy and liver development differ dramatically with regard to transcription factors and chromatin structure modification. In contrast, the tissues are similar with regard to proliferation-associated genes. Consistent with these findings, real-time polymerase chain reaction showed transcription factors known to be important in liver development are not induced during liver regeneration. These three lines of evidence suggest that at a transcriptional level restoration of liver mass after injury is best described as hepatocyte hyperplasia and not true regeneration. We speculate this novel pattern of gene expression may underlie the unique capacity of the liver to repair itself after injury.

Analysis of differential gene expression in Litopenaeus vannamei under High salinity stress

Editor's evaluation: Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria

Introduction: Breast cancers differ between genomic and transcriptomic features by ancestry within the TCGA, but current understanding of how gene expression differs across global ancestral populations is extremely limited. We hypothesized that differential expression performed by ancestry and geography may provide insight into population-specific, clinically relevant expression patterns. Objective: To compare differentially expressed protein-coding genes and pathways among primary breast tumors of Nigerian origin versus African- and European-American ancestry in TCGA Methods: We analyzed an integrated dataset of RNA-seq from 93 women in Nigeria, 31 African-ancestry women (TCGA AA), and 39 European-ancestry women from TCGA (TCGA EA) with whole-genome data. Ancestry within TCGA was classified by principal component analysis, with African ancestry as >50% contribution and European ancestry as >90% contribution. RNA was obtained from tumors in Nigeria using Qiagen PAXgene kits. A STAR/HTSeq pipeline generated read counts. To optimize assay-associated batch effects, we performed differential expression within each PAM50 subtype using limma-voom with quantile normalization. Significance was defined as a > 1.5-fold change in gene expression (log2 scale) with a false-discovery-rate-adjusted p-value of 0.05. Pathway analysis was performed via Gene Ontology and the Web-Based Gene Set Analysis Toolkit. We also compared gene expression, claudin-low (30 genes) and VEGF (13 genes) signatures to an additional set of 189 primary breast cancers from Nigeria assayed on the NanoString nCounter System using a custom Nano110 probe set (PAM50 + claudin-low & VEGF genes). RNA for these cancers was isolated from paraffin-embedded tumor using the Roche High Pure paraffin kit. Results: Differential expression was performed pairwise across ancestry groups within PAM50 subtypes (see Table). Fewer genes were differentially expressed, and fold change smaller across shared genes, when comparing Nigerian vs. TCGA AA versus Nigerian vs. TCGA EA comparisons, supporting quantile normalization. The strongest gene ontology pathway associations, seen for all subtypes, were intracellular protein targeting and viral gene expression. The epigenetic regulation pathway was significantly associated with comparisons in Basal-like tumors (padj=1.54e-7 for TCGA EA, padj=0.001 for TCGA AA). The PI3K-Akt pathway was significantly associated with Nigerian vs. TCGA-EA within Luminal A (padj=0.006). The Nanostring cohort shared a similar distribution of PAM50 subtypes (see Table, X2 p=0.21). We found concordance in both Nigerian cohorts of relative claudin-low and VEGF expression signature patterns across subtypes. Of 17 genes with significant differential expression by ancestry in the Nanostring dataset, 9 (ADM, ACTB, BIRC5, CDC6, CENPF, MKI67, MPP1, RAD17, and VEGFA) showed significant differential expression by ancestry in the PAXgene dataset. Discussion: This is one of the first analyses of differential gene expression across tumors from a global population. We identified differential pathways in breast tumors between African and European ancestry populations to target for future work. We also validated several ancestry-specific genes across platforms with potential clinical relevance. Understanding how molecular features differ across global populations will improve precision oncology for all patients. PAM50ClassificationNigerian: PAXgene (n=93)TCGA AA (n=31)TCGA EA (n=39)Nigerian: Nanostring (n=189)Nigerian (PAXgene) vs. TCGA EA ComparisonNigerian (PAXgene) vs. TCGA AAComparisonBasal-like41 (42.8%)23 (74.1%)17 (43.6%)78 (41.3%)4893 genes4687 genesHer2-enriched27 (28.1%)05 (12.8%)31 (16.4%)961 genesN/ALuminal A14 (14.5%)4 (12.9%)8 (20.5%)39 (20.6%)2596 genes480 genesLuminal B11 (11.4%)4 (12.9%)9 (23.1%)25 (13.2%)2112 genes222 genes Citation Format: Padma Sheila Rajagopal, Yi-Hsuan S Tsai, Ashley Hardeman, Ian Hurley, Aminah Sallam, Yonglan Zheng, Toshio Yoshimatsu, Anna Woodard, Dezheng Huo, Guimin Gao, Charles M Perou, Joel S Parker, Mengjie Chen, Olufunmilayo I Olopade. Comparative analysis of differential gene expression by ancestry using primary breast cancers from Nigeria and the cancer genome atlas (TCGA) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-12.

Arthritis susceptibility genes were sought by analysis of differential gene expression between pristane-induced arthritis (PIA)-susceptible DA rats and PIA-resistant E3 rats. Inguinal lymph nodes of naïve animals and animals 8 days after pristane injection were analyzed for differential gene expression. mRNA expression was investigated by microarray and real-time PCR, and protein expression was analyzed by flow cytometry or ELISA. Twelve genes were significantly differentially expressed when analyzed by at least two independent methods, and an additional five genes showed a strong a tendency toward differential expression. In naïve DA rats IgE, the bone marrow stromal cell antigen 1 (Bst1) and the MHC class II β-chain (MhcII) were expressed at a higher level, and the immunoglobulin kappa chain (Igκ) was expressed at a lower level. In pristane-treated DA rats the MHC class II β-chain, gelatinase B (Mmp9) and the protein tyrosine phosphatase CL100 (Ptpn16) were expressed at a higher level, whereas immunoglobulins, the CD28 molecule (Cd28), the mast cell specific protease 1 (Mcpt1), the carboxylesterase precursor (Ces2), K-cadherin (Cdh6), cyclin G1 (Ccng1), DNA polymerase IV (Primase) and the tumour associated glycoprotein E4 (Tage) were expressed at a lower level. Finally, the differentially expressed mRNA was confirmed with protein expression for some of the genes. In conclusion, the results show that animal models are well suited for reproducible microarray analysis of candidate genes for arthritis. All genes have functions that are potentially important for arthritis, and nine of the genes are located within genomic regions previously associated with autoimmune disease.

Longitudinal Effects of 1-Year Smoking Cessation on Human Bronchial Epithelial Transcriptome

T-cell acute lymphoblastic leukemia (T-ALL) is a malignancy of immature T-cells characterized by rapid proliferation of leukemic cells in the bone marrow and blood. Despite significant advancements in the understanding and treatment of B-cell acute lymphoblastic leukemia (B-ALL), T-ALL remains comparatively underexplored, with limited data on the underlying genomic alterations driving disease progression. T-ALL constitutes 12-15% of pediatric and adult ALL cases, with poorer outcomes than B-ALL. Understanding differential gene expression in T-ALL is critical, especially with respect to how these may differ across racial groups, as African Americans and Asians have been shown to have lower survival than Caucasians. In this study, we analyzed RNA sequencing data from a cohort of pediatric T-ALL patients to identify differences in gene expression patterns between racial groups, specifically focusing on Caucasian, Asian, and African American patients. Using DESeq2, differential gene expression analysis was performed across racial categories. A total of 37 patients with genomic data were included, with expression counts normalized, and statistical significance was determined based on adjusted p-values <0.05. We also examined potential correlations between gene expression and clinical outcomes such as relapse status. Preliminary results identified several genes exhibiting significant differential expression between racial groups. 250 genes, mostly related to the adaptive immune system, were significantly differentially expressed in Caucasian vs African American patients. 261 genes, mostly related to homeostasis and cellular development, showed differential expression in Caucasian vs Asian patients. There was an overlap of 17 genes which were differentially expressed in all three races. Importantly, FAT1 was one of these 17 genes, as it is a gene that has previously been implicated in T-ALL but not studied with regard to differences in expression by race. Preliminary analyses also found differentially expressed genes between African American vs Asian and relapse vs non-relapse. Additional studies are ongoing to determine the specificity of all these genes to T-ALL and to compare the genes that were differentially expressed across various races to the genes differentially expressed across outcomes. This study highlights the importance of examining racial differences in gene expression within T-ALL, a leukemia subtype that has not been extensively understood. The identification of race-specific gene expression profiles may provide insights into the biological mechanisms that contribute to differences in clinical outcomes and response to treatment. Future work will focus on validating these findings in larger, independent cohorts and exploring how these genetic differences may influence disease progression, ultimately reducing racial disparities in T-ALL survival. Citation Format: Rishabh Gaur, Irina Pushel, Midhat Farooqi. Differences in gene expression across races in pediatric T-cell acute lymphoblastic leukemia (T-ALL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 505.

This study was designed to examine the effect of enzyme replacement therapy (ERT) on differential gene expression in peripheral blood mononuclear cells (PBMCs) of children with Fabry disease who had not previously been exposed to ERT. Thirteen children with Fabry disease (age range, 6.5-17.0 years) were studied as part of a 6-month, open-label study of ERT with agalsidase alfa. Paired blood samples were taken at the start of the study and after 6 months of ERT. Further blood samples were also taken from 16 age-matched control subjects. PBMCs were isolated and, following RNA extraction, differential gene expression analysis was performed using the Human Genome U133 Plus 2.0 microarray. Twenty-one genes were determined to be differentially expressed in PBMCs of ERT-naïve children with Fabry disease compared with healthy controls; neuronal apoptosis inhibitory protein ranked as the most significantly differentially expressed gene. Comparison of gene expression in children with Fabry disease prior to and after ERT showed that two genes were significantly differentially expressed (p < or = 0.05) following treatment; the expressed sequence tag (probe set ID, 243259_at) was downregulated, while expression of apoptosis-inducing factor was increased, possibly as an antioxidant counter-regulatory response. This study identifies a number of genes that are differentially expressed in a small cohort of children with Fabry disease relative to healthy controls. These genes may relate to the underlying biological abnormalities in Fabry disease.

Identification of differentially expressed genes in gills of tiger puffer (Takifugu rubripes) in response to low-salinity stress.

3073Leveraging transcriptome sequencing for detecting novel disease-related pathways using human cardiac sarcoidosis myocardium biopsies

Differential gene expression before and after ionizing radiation of subcutaneous fibroblasts identifies breast cancer patients resistant to radiation-induced fibrosis

Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis

RNA-Sequencing (RNA-Seq) is performed to measure gene expression, often to ask the question of what genes are differentially expressed across various biological conditions. Statistical methods have been used to model RNA-Seq quantifications in order to determine differential expression, and have traditionally be divided into gene-level methods and transcript-level methods. There has been little attempt to connect the statistical divide, although transcript expression and gene expression are biologically inextricably linked. In this thesis, we provide a case study of a comparative differential expression analysis, demonstrating that many differential expression events happen on the isoform-level, and that performing an analysis using only summarized gene quantifications would fail to capture these events. Furthermore, we develop statistical methods that unify the transcript-level and gene-level analysis. In bulk RNA-Seq, by using p-value aggregation methods, we are able to translate transcript-level results into gene-level results under a unified framework. For single cell RNA-Seq, we propose using multiple logistic regression, leveraging the high dimensionality of the data in order to determine if the transcript quantifications pertaining to a gene are able to constitute a linear discriminant for cell type. This method combines differential transcript expression analysis and differential gene expression analysis into a unified framework which we call “gene differential expression.” Lastly, we demonstrate that our methods could be used on transcript compatibility counts instead of transcript quantifications in order to bypass ambiguous read assignment and improve accuracy. We show that transcript compatibility counts obtained via transcriptome pseudoalignment are comparable in quantification accuracy to quantifications from genome alignment methods.

Background: Invasive lobular carcinoma (ILC) comprises 10-15% of breast tumors and is the second most common histological type after invasive ductal carcinoma (IDC). Patients with ILC are often diagnosed at an older age and more advanced stage than those with IDC. Late recurrences and worse long-term survival suggest the need for improved approaches to treatment optimization and exploration of molecular pathways unique to ILC. Although previous reports have described comprehensive transcriptomic profiling of ILC, these were limited by small sample sizes. Furthermore, differential gene expression between ILC and IDC within genomic risk groups and molecular subtypes has yet to be explored. Here we characterize differential gene expression between ILC and IDC in a large, age-matched patient subset categorized by 70-gene signature/MammaPrint (MP) risk and 80-gene signature/BluePrint (BP) subtype. Methods: The prospective FLEX Registry (NCT03053193) includes stage I-III primary invasive breast cancer patients who receive MP/BP testing and consent to full transcriptome and clinical data collection. This sub-analysis included 450 ILC patients enrolled from 2017 to present. Compared with a random selection of IDC patients (n=450, mean age, 60 years), ILC patients were older (mean, 63 years, p&amp;lt;0.001). Thus, we selected an age-matched subset for differential gene expression analysis. There were few non-Luminal ILCs; thus, gene expression analyses were limited to BP Luminal tumors. A subset of 413 age-matched pairs (n=826) of ILC and IDC were used for analysis. Gene expression data were quantile normalized using R limma package, and differentially expressed genes (DEGs) were compared between groups. DEGs with an adjusted p&amp;lt;0.05 and log2 fold change &amp;gt; ± 1.0 were considered significant. Results: ILC represented 13% of FLEX cases (n=450/3562), and were 81% lymph node-negative, 99% ER+, 94% HER2-negative, and 68% MP Low Risk (LR). By BP, ILC were 99% Luminal, 1% HER2, and &amp;lt;1% Basal type. BP Luminal ILC were predominantly grade 2 (63%), T1 (61%), node-negative (84%), and MP LR (69%). Menopausal status, nodal status, ethnicity, BMI distribution, and frequency of type 2 diabetes mellitus were similar between ILC and IDC. However, IDC were more likely to be MP HR (46% IDC vs. 31% ILC, p&amp;lt;0.001) and grade 3 (15% IDC vs. 4% ILC, p&amp;lt;0.001). ILC were more likely to be T3 (10% ILC vs. 1% IDC, p&amp;lt;0.001). We found 4 DEGs common to all comparisons: all Luminal ILC vs. IDC, MP LR ILC vs. IDC, and MP HR ILC vs. IDC. ILC had lower expression of CDH1 (E-cadherin) than IDC, regardless of MP risk. Including CDH1, 6 unique genes were differentially expressed in LR ILC compared with IDC, and 21 genes were differentially expressed in HR ILC compared with IDC. Genes with increased expression in HR ILC were related to immune cell migration/chemotaxis, hormone signaling, and growth factor signaling. HR ILCs were also enriched for TGFβ signaling and angiogenesis pathway genes. Conclusions: Here we report differential clinical and molecular characteristics between ILC and IDC in a large, age-matched patient subset. Regardless of MP risk, expression of CDH1 was lower in ILC compared with IDC. Approximately one-third of ILCs were MP HR, and we report a greater number and diversity of DEGs between HR ILC and HR IDC compared with LR tumors, in particular genes related to TGFβ signaling. TGFβ pathway genes play a variety of roles in the tumor microenvironment, including induction of angiogenesis, fibroblast growth factor stimulation, and inhibition and/or exclusion of an immune response. These results suggest that therapeutic strategies targeting the TGFβ pathway may be future avenues of exploration in ILC, although further studies are warranted to characterize underlying molecular mechanisms. Citation Format: Beth-Ann Lesnikoski, Jennifer A. Crozier, Gordan Srkalovic, Patricia Robinson, Clodia Osipo, Kaylan Banda, Heather M. Kling, Josien Haan, William Audeh, FLEX Investigators Group. Differential gene expression in luminal-type invasive lobular carcinoma and invasive ductal carcinoma by MammaPrint risk stratification [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-03.