Transcriptomal analysis of failing and nonfailing human hearts

2003 ◽  
Vol 12 (2) ◽  
pp. 97-112 ◽  
Author(s):  
M. Steenman ◽  
Y.-W. Chen ◽  
M. Le Cunff ◽  
G. Lamirault ◽  
A. Varró ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiac Function ◽  
Expression Profile ◽  
Large Scale ◽  
Expression Profiles ◽  
Statistical Tests ◽  
Differentially Expressed ◽  
Developmental Gene Expression ◽  
Similar Expression Profile

Heart failure is a multifactorial disease that may result from different initiating events. To contribute to an improved comprehension of normal cardiac function and the molecular events leading to heart failure, we performed large-scale gene expression analysis of failing and nonfailing human ventricle. Our aim was to define and compare expression profiles of 4 specific pathophysiological cardiac situations: 1) left ventricle (LV) from nonfailing heart; 2) LV from failing hearts affected by dilated cardiomyopathy (DCM); 3) LV from failing hearts affected by ischemic CM (ICM); 4) right ventricle (RV) from failing hearts affected by DCM or ICM. We used oligonucleotide arrays representing ∼12,000 human genes. After stringent numerical analyses using several statistical tests, we identified 1,306 genes with a similar expression profile in all 4 cardiac situations, therefore representative of part of the human cardiac expression profile. A total of 95 genes displayed differential expression between failing and nonfailing heart samples, reflecting a reversal to developmental gene expression, dedifferentiation of failing cardiomyocytes, and involvement of apoptosis. Twenty genes were differentially expressed between failing LV and failing RV, identifying possible candidates for different functioning of both ventricles. Finally, no genes were found to be significantly differentially expressed between failing DCM and failing ICM LV, emphasizing that transcriptomal analysis of explanted hearts results mainly in identification of expression profiles of end-stage heart failure and less in determination of expression profiles of the underlying etiology. Taken together, our data resulted in identification of putative transcriptomal landmarks for normal and disturbed cardiac function.

Differential myocardial gene expression in the development and rescue of murine heart failure

2003 ◽  
Vol 15 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Burns C. Blaxall ◽  
Rainer Spang ◽  
Howard A. Rockman ◽  
Walter J. Koch
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiac Function ◽  
Predictive Model ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Expression Profiles ◽  
Left Ventricular ◽  
Statistical Analyses ◽  
Cardiac Phenotype

Numerous murine models of heart failure (HF) have been described, many of which develop progressive deterioration of cardiac function. We have recently demonstrated that several of these can be “rescued” or prevented by transgenic cardiac expression of a peptide inhibitor of the β-adrenergic receptor kinase (βARKct). To uncover genomic changes associated with cardiomyopathy and/or its phenotypic rescue by the βARKct, oligonucleotide microarray analysis of left ventricular (LV) gene expression was performed in a total of 53 samples, including 12 each of Normal, HF, and Rescue. Multiple statistical analyses demonstrated significant differences between all groups and further demonstrated that βARKct Rescue returned gene expression toward that of Normal. In our statistical analyses, we found that the HF phenotype is blindly predictable based solely on gene expression profile. To investigate the progression of HF, LV gene expression was determined in young mice with mildly diminished cardiac function and in older mice with severely impaired cardiac function. Interestingly, mild and advanced HF mice shared similar gene expression profiles, and importantly, the mild HF mice were predicted as having a HF phenotype when blindly subjected to our predictive model described above. These data not only validate our predictive model but further demonstrate that, in these mice, the HF gene expression profile appears to already be set in the early stages of HF progression. Thus we have identified methodologies that have the potential to be used for predictive genomic profiling of cardiac phenotype, including cardiovascular disease.

Regional variations in ABC transporter expression along the mouse intestinal tract

2004 ◽  
Vol 17 (1) ◽  
pp. 11-20 ◽  
Author(s):  
David M. Mutch ◽  
Pascale Anderle ◽  
Muriel Fiaux ◽  
Robert Mansourian ◽  
Karine Vidal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Abc Transporter ◽  
Expression Profile ◽  
Abc Transporters ◽  
Intestinal Tract ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Assessment Model ◽  
Differentially Expressed ◽  
Distal Intestine

The ATP-binding cassette (ABC) family of proteins comprise a group of membrane transporters involved in the transport of a wide variety of compounds, such as xenobiotics, vitamins, lipids, amino acids, and carbohydrates. Determining their regional expression patterns along the intestinal tract will further characterize their transport functions in the gut. The mRNA expression levels of murine ABC transporters in the duodenum, jejunum, ileum, and colon were examined using the Affymetrix MuU74v2 GeneChip set. Eight ABC transporters (Abcb2, Abcb3, Abcb9, Abcc3, Abcc6, Abcd1, Abcg5, and Abcg8) displayed significant differential gene expression along the intestinal tract, as determined by two statistical models (a global error assessment model and a classic ANOVA, both with a P < 0.01). Concordance with semiquantitative real-time PCR was high. Analyzing the promoters of the differentially expressed ABC transporters did not identify common transcriptional motifs between family members or with other genes; however, the expression profile for Abcb9 was highly correlated with fibulin-1, and both genes share a common complex promoter model involving the NFκB, zinc binding protein factor (ZBPF), GC-box factors SP1/GC (SP1F), and early growth response factor (EGRF) transcription binding motifs. The cellular location of another of the differentially expressed ABC transporters, Abcc3, was examined by immunohistochemistry. Staining revealed that the protein is consistently expressed in the basolateral compartment of enterocytes along the anterior-posterior axis of the intestine. Furthermore, the intensity of the staining pattern is concordant with the expression profile. This agrees with previous findings in which the mRNA, protein, and transport function of Abcc3 were increased in the rat distal intestine. These data reveal regional differences in gene expression profiles along the intestinal tract and demonstrate that a complete understanding of intestinal ABC transporter function can only be achieved by examining the physiologically distinct regions of the gut.

scholarly journals Gene Expression Profiles of Papillary Thyroid Microcarcinoma

2017 ◽  
Vol 102 (1-2) ◽  
pp. 39-46 ◽  
Author(s):  
Woo Young Kim ◽  
Jae Bok Lee ◽  
Seung Pil Jung ◽  
Hoon Yub Kim ◽  
Sang Uk Woo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Differentially Expressed Genes ◽  
Expression Profile ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Papillary Thyroid Microcarcinoma ◽  
Papillary Thyroid ◽  
Normal Thyroid ◽  
Thyroid Microcarcinoma

The objective was to identify gene expression profile of papillary thyroid microcarcinoma. To help improve diagnosis of papillary thyroid microcarcinoma, we performed gene expression profiling and compared it to pair normal thyroid tissues. We performed microarray analysis with 6 papillary thyroid microcarcinoma and 6 pair normal thyroid tissues. Differentially expressed genes were selected using paired t test, linear models for microarray data, and significance analysis of microarrays. Real-time quantitative reverse transcription–polymerase chain reaction was used to validate the representative 10 genes (MET, TIMP1, QPCT, PROS1, LRP4, SDC4, CITED1, DPP4, LRRK2, RUNX2). We identified 91 differentially expressed genes (84 upregulated and 7 downregulated) in the gene expression profile and validated 10 genes of the profile. We identified a significant genetic difference between papillary thyroid microcarcinoma and normal tissue by 10 upregulated genes greater than 2-fold (P &lt; 0.05).

The Challenge of Using CB-HSCs As Source for Gene Therapy: Lentiviral Vector Transduction, Phenotypic Characterization and Global Gene Expression Profile of Ex-Vivo Expanded CB CD34+ Cells

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5548-5548
Author(s):  
Rosalia Di Stefano ◽  
Elena Baiamonte ◽  
Melania Lo Iacono ◽  
Barbara Spina ◽  
Flavia Contino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Expression Profiles ◽  
Culture Conditions ◽  
Differentially Expressed ◽  
Cd34 Cells

Abstract Introduction: Genetic modification of autologous hematopoietic stem and progenitor cells (HSPC) is a promising clinical intervention to cure inherited monogenic diseases. Successful gene therapy trials have already been conducted using CD34+ cells from bone marrow and from mobilized peripheral blood. In this regard, cord blood (CB) represents an attractive source of HSCs due to its high concentration of high proliferative HSPC and increased susceptibility to be transduced by lentiviral vectors. Unfortunately, the major disadvantage is the limited number of HSC in the CB collection. Consequently, ex-vivo expansion of CB-HSC is desirable to extend clinical applications. Purposes: To investigate the ability of UCB-cd34+ cells to be expanded in serum-free media supplemented with the early acting hematopoietic cytokines SCF,TPO and Flt-3 ligant (STF) and to characterize CD34+ cells subtypes, clonogenic capacity and gene expression profile during expansion. We also wanted to investigate the susceptibility of the expanded cd34+ cells to be transduced by a GFP-lentiviral vector (LV-GFP) Material and Methods: CD34+ immunoselected cells from 10 UCB were grown for 8 days in customized serum-free medium formulated for HSC expansion, supplemented with STF cytokines. Numbers end frequency of CD34+cells and co-expression of the primitive surface antigens (CD38, CD133, CD90) was evaluated during expansion. Colonies developed in methylcellulose were scored for enumeration ad typing. LV-GFP transduction efficiency was evaluated in CD34+ cells cultured for 4 days in expansion medium plus STF and for 24 hrs in X-vivo10 medium with STF±IL-3 cytokines; the last condition slightly expands CD34+ cells (1.3 fold) and are currently used for HSPC-lentivector transduction in gene therapy clinical trials. The transduction efficiency was evaluated by measuring the percentage of GFP+ cells in the bulk and in colonies developed in methylcellulose and the VCN/cell by Q-PCR. Gene expression profiles were analyzed by human whole genome Agilent microarray Technology to detect differentially expressed genes between expanded, ex-vivo medium cultured and un-cultured cells. Results: We found an average of 8 fold-increase CD34+cells at day 4 and of 22 fold- increase at day 8 of culture. The frequency of CD34+ was maintained at day 4 and declined of about 50% at day 8. CD34+/CD38- early progenitors doublet as early as day 4, differences in CD34+/CD133+ and CD34+/CD90+cells were not significant. The number of CFU slightly increased during expansion while the relative frequency of colonies type did not significantly changed. Four days expanded CD34+ cells were transduced more efficiently than those grown in ex-vivo medium even in presence of IL-3 added to the STF cytokine cocktail. Comprehensive gene expression profile analysis highlighted about 4000 genes differentially expressed in CD34+ cells expanded for 4 and for 8 days compared to that of the un-cultured cells. Conversely, the expression profiles analysis did not show any clear separation between different cell culture methods (expansion vs ex-vivo medium). Specifically, the number of differentially expressed genes in common between the different culture conditions compared with the un-cultured cells was statistically significant. Unsurprisingly, the common up-regulated genes were related to the cell cycle. The likeness between the gene expression profiles of the different culture conditions was also validated by the identification of a significantly small number of differentially expressed genes between them. Conclusions: UCB-CD34+ cells can be efficiently expanded and transduced in serum free conditions. The expanded cells exhibited phenotypic marchers typical of early progenitors and developed colonies in number and in type similar to the unmanipulated cells and exhibited whole gene expression profile that is consisted with that of CD34+ cells exposed for the short term culture conditions currently used in gene therapy trial mediated by lentiviral vectors. Results from this study open a window on the future possibility of using homologous UCB-HSC as target for gene correction in patients diagnosed for a genetic disorder in prenatal time. The genetically modified cells would be stored and used for gene therapy in the same individual in pediatric age. This work was funded by the F and P Cutino Foundation - Project RiMedRi CUP G73F12000150004 Disclosures No relevant conflicts of interest to declare.

196 EMBRYO BIOPSY TRANSCRIPTOMICS: A POTENTIAL TOOL TO IDENTIFY TRANSCRIPTS DIRECTLY RELATED TO THE ABILITY OF THE EMBRYO TO INDUCE PREGNANCY AFTER TRANSFER

2009 ◽  
Vol 21 (1) ◽  
pp. 196
Author(s):  
D. Tesfaye ◽  
N. Ghanem ◽  
F. Rings ◽  
E. Tholen ◽  
C. Phatsara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pregnancy Outcome ◽  
Expression Profile ◽  
Expression Profiles ◽  
Transcript Abundance ◽  
Differentially Expressed ◽  
Embryo Biopsy ◽  
Bovine Embryo

The incidence of pregnancy loss due to embryonic mortality in cattle is one of the major causes of reproductive failure. The early embryonic loss can be due to problems with the embryo itself, the uterine environment, or interactions between the embryo and the uterus. So, this study was conducted to investigate the gene expression profile of bovine embryo biopsies produced in vivo and in vitro that resulted in different pregnancy outcomes. For this, biopsies representing 30 to 40% of the intact in vitro and in vivo blastocysts were taken, and 60 to 70% part was allowed to re-expand prior to transfer to recipients. Based on the pregnancy outcome after transfer, biopsies (n = 10 per pool) were grouped into 3 distinct phenotypes: those that resulted in no pregnancy, those that resulted in resorption, and those that resulted in successful pregnancy and subsequent calf delivery. A bovine cDNA microarray with 2000 clones was used to analyze the gene expression profiles of 3 replicates from each embryo biopsy group. Array data analysis revealed a total of 50 and 52 genes to be differentially expressed between biopsies derived from in vivo blastocysts that resulted in no pregnancy v. calf delivery and resorption v. calf delivery, respectively. Similarly, a total of 52 and 58 transcripts were differentially expressed between biopsies derived from in vitro-produced blastocysts that resulted in no pregnancy v. calf delivery and resorption v. calf delivery, respectively. Quantitative real-time PCR has confirmed the expression profile of 6 selected candidate genes. A distinct set of genes were found to be commonly expressed between in vitro- and in vivo-derived blastocyst biopsies, which ended up with the same pregnancy outcome. Biopsies, which ended up with calf delivery, were found to be enriched with transcripts involved in nucleosome assembly (KRT8), translation (RPLPO), electron transport (COX-2), and placenta specific (PLAC8). On the other hand, transcripts regulating immune response (TNFa), response to stress (HSPD1), and cell adhesion (CD9) were up-regulated in embryos that resulted in no pregnancy or resorption. Differences in transcript abundance of some genes have been seen between biopsies derived from in vitro and in vivo blastocysts. Biopsies from in vivo-derived blastocysts and that ended up with resorption were found to be enriched with transcripts regulating calcium-binding protein (S100A10, S100A14). Transcription factor-related transcripts (CDX2, HOXB7) were up-regulated in vitro-derived blastocyst biopsies that resulted in no pregnancy. In conclusion, the results evidenced that embryos derived from either in vitro or in vivo have more similarities than differences in their transcript abundance with respect to the ability in initiating pregnancy.

scholarly journals Construction and analysis of mRNA, miRNA, lncRNA, and TF regulatory networks reveal the key genes in prostate cancer

2018 ◽  
Author(s):  
Su-Liang Li ◽  
Yun Ye ◽  
Sheng-Yu Wang
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Scale Effects ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Regulation Of Transcription ◽  
Normal Prostate ◽  
Ppi Networks

AbstractPurpose: Prostate cancer (PCa) causes a common male urinary system malignant tumour, and the molecular mechanisms of PCa remain poorly understood. This study aims to investigate the underlying molecular mechanisms of PCa with bioinformatics.Methods: Original gene expression profiles were obtained from the GSE64318 and GSE46602 datasets in the Gene Expression Omnibus (GEO). We conducted differential screens of the expression of genes (DEGs) between two groups using the R software limma package. The interactions between the differentially expressed miRNAs, mRNAs and lncRNAs were predicted and merged with the target genes. Co-expression of the miRNAs, lncRNAs and mRNAs were selected to construct the mRNA-miRNA and-lncRNA interaction networks. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the DEGs. The protein-protein interaction (PPI) networks were constructed, and the transcription factors were annotated. The expression of hub genes in the TCGA datasets was verified to improve the reliability of our analysis.Results: The results demonstrated that 60 miRNAs, 1578 mRNAs and 61 lncRNAs were differentially expressed in PCa. The mRNA-miRNA-lncRNA networks were composed of 5 miRNA nodes, 13 lncRNA nodes, and 45 mRNA nodes. The DEGs were mainly enriched in the nuclei and cytoplasm and were involved in the regulation of transcription, related to sequence-specific DNA binding, and participated in the regulation of the PI3K-Akt signalling pathway. These pathways are related to cancer and focal adhesion signalling pathways. Furthermore, we found that 5 miRNAs, 6 lncRNAs, 6 mRNAs and 2 TFs play important regulatory roles in the interaction network. The expression levels of EGFR, VEGFA, PIK3R1, DLG4, TGFBR1 and KIT were significantly different between PCa and normal prostate tissue.Conclusion: Based on the current study, large-scale effects of interrelated mRNAs, miRNAs, lncRNAs, and TFs were revealed and a model for predicting the mechanism of PCa was provided. This study provides new insight for the exploration of the molecular mechanisms of PCa and valuable clues for further research.

scholarly journals Comprehensive Comparison of Amnion Stromal Cells and Chorion Stromal Cells by RNA-Seq

2021 ◽  
Vol 22 (4) ◽  
pp. 1901
Author(s):  
Brielle Jones ◽  
Chaoyang Li ◽  
Min Sung Park ◽  
Anne Lerch ◽  
Vimal Jacob ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stromal Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Principal Component ◽  
Differentially Expressed ◽  
Inflammatory Factor ◽  
Next Generation Sequencing Technology ◽  
Angiogenic Potential ◽  
Anti Inflammatory

Mesenchymal stromal cells derived from the fetal placenta, composed of an amnion membrane, chorion membrane, and umbilical cord, have emerged as promising sources for regenerative medicine. Here, we used next-generation sequencing technology to comprehensively compare amniotic stromal cells (ASCs) with chorionic stromal cells (CSCs) at the molecular and signaling levels. Principal component analysis showed a clear dichotomy of gene expression profiles between ASCs and CSCs. Unsupervised hierarchical clustering confirmed that the biological repeats of ASCs and CSCs were able to respectively group together. Supervised analysis identified differentially expressed genes, such as LMO3, HOXA11, and HOXA13, and differentially expressed isoforms, such as CXCL6 and HGF. Gene Ontology (GO) analysis showed that the GO terms of the extracellular matrix, angiogenesis, and cell adhesion were significantly enriched in CSCs. We further explored the factors associated with inflammation and angiogenesis using a multiplex assay. In comparison with ASCs, CSCs secreted higher levels of angiogenic factors, including angiogenin, VEGFA, HGF, and bFGF. The results of a tube formation assay proved that CSCs exhibited a strong angiogenic function. However, ASCs secreted two-fold more of an anti-inflammatory factor, TSG-6, than CSCs. In conclusion, our study demonstrated the differential gene expression patterns between ASCs and CSCs. CSCs have superior angiogenic potential, whereas ASCs exhibit increased anti-inflammatory properties.

4 Molecularly guided multiplexed digital spatial analysis reveals differential gene expression profiles in the WNT-β-catenin pathway between melanoma and prostate tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A4-A4
Author(s):  
Anushka Dikshit ◽  
Dan Zollinger ◽  
Karen Nguyen ◽  
Jill McKay-Fleisch ◽  
Kit Fuhrman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Single Molecule ◽  
Spatial Information ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Fluorescence Assay ◽  
Differentially Expressed ◽  
Tumor Type ◽  
Prostate Tumors

BackgroundThe canonical WNT-β-catenin signaling pathway is vital for development and tissue homeostasis but becomes strongly tumorigenic when dysregulated. and alter the transcriptional signature of a cell to promote malignant transformation. However, thorough characterization of these transcriptomic signatures has been challenging because traditional methods lack either spatial information, multiplexing, or sensitivity/specificity. To overcome these challenges, we developed a novel workflow combining the single molecule and single cell visualization capabilities of the RNAscope in situ hybridization (ISH) assay with the highly multiplexed spatial profiling capabilities of the GeoMx™ Digital Spatial Profiler (DSP) RNA assays. Using these methods, we sought to spatially profile and compare gene expression signatures of tumor niches with high and low CTNNB1 expression.MethodsAfter screening 120 tumor cores from multiple tumors for CTNNB1 expression by the RNAscope assay, we identified melanoma as the tumor type with the highest CTNNB1 expression while prostate tumors had the lowest expression. Using the RNAscope Multiplex Fluorescence assay we selected regions of high CTNNB1 expression within 3 melanoma tumors as well as regions with low CTNNB1 expression within 3 prostate tumors. These selected regions of interest (ROIs) were then transcriptionally profiled using the GeoMx DSP RNA assay for a set of 78 genes relevant in immuno-oncology. Target genes that were differentially expressed were further visualized and spatially assessed using the RNAscope Multiplex Fluorescence assay to confirm GeoMx DSP data with single cell resolution.ResultsThe GeoMx DSP analysis comparing the melanoma and prostate tumors revealed that they had significantly different gene expression profiles and many of these genes showed concordance with CTNNB1 expression. Furthermore, immunoregulatory targets such as ICOSLG, CTLA4, PDCD1 and ARG1, also demonstrated significant correlation with CTNNB1 expression. On validating selected targets using the RNAscope assay, we could distinctly visualize that they were not only highly expressed in melanoma compared to the prostate tumor, but their expression levels changed proportionally to that of CTNNB1 within the same tumors suggesting that these differentially expressed genes may be regulated by the WNT-β-catenin pathway.ConclusionsIn summary, by combining the RNAscope ISH assay and the GeoMx DSP RNA assay into one joint workflow we transcriptionally profiled regions of high and low CTNNB1 expression within melanoma and prostate tumors and identified genes potentially regulated by the WNT- β-catenin pathway. This novel workflow can be fully automated and is well suited for interrogating the tumor and stroma and their interactions.GeoMx Assays are for RESEARCH ONLY, not for diagnostics.

scholarly journals LncGSEA: a versatile tool to infer lncRNA associated pathways from large-scale cancer transcriptome sequencing data

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanan Ren ◽  
Ting-You Wang ◽  
Leah C. Anderton ◽  
Qi Cao ◽  
Rendong Yang
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Clinical Samples ◽  
Sequencing Data ◽  
Multiple Cancer ◽  
Regulatory Pathways ◽  
Cancer Transcriptome ◽  
Versatile Tool

Abstract Background Long non-coding RNAs (lncRNAs) are a growing focus in cancer research. Deciphering pathways influenced by lncRNAs is important to understand their role in cancer. Although knock-down or overexpression of lncRNAs followed by gene expression profiling in cancer cell lines are established approaches to address this problem, these experimental data are not available for a majority of the annotated lncRNAs. Results As a surrogate, we present lncGSEA, a convenient tool to predict the lncRNA associated pathways through Gene Set Enrichment Analysis of gene expression profiles from large-scale cancer patient samples. We demonstrate that lncGSEA is able to recapitulate lncRNA associated pathways supported by literature and experimental validations in multiple cancer types. Conclusions LncGSEA allows researchers to infer lncRNA regulatory pathways directly from clinical samples in oncology. LncGSEA is written in R, and is freely accessible at https://github.com/ylab-hi/lncGSEA.

scholarly journals Predicting Host Immune Cell Dynamics and Key Disease-Associated Genes Using Tissue Transcriptional Profiles

Processes ◽  
2019 ◽  
Vol 7 (5) ◽  
pp. 301
Author(s):  
Muying Wang ◽  
Satoshi Fukuyama ◽  
Yoshihiro Kawaoka ◽  
Jason E. Shoemaker
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Immune Cell ◽  
Mean Squared Error ◽  
Expression Profiles ◽  
Statistical Tests ◽  
Critical Factor ◽  
Expression Data ◽  
Cell Dynamics ◽  
Cell Counts

Motivation: Immune cell dynamics is a critical factor of disease-associated pathology (immunopathology) that also impacts the levels of mRNAs in diseased tissue. Deconvolution algorithms attempt to infer cell quantities in a tissue/organ sample based on gene expression profiles and are often evaluated using artificial, non-complex samples. Their accuracy on estimating cell counts given temporal tissue gene expression data remains not well characterized and has never been characterized when using diseased lung. Further, how to remove the effects of cell migration on transcript counts to improve discovery of disease factors is an open question. Results: Four cell count inference (i.e., deconvolution) tools are evaluated using microarray data from influenza-infected lung sampled at several time points post-infection. The analysis finds that inferred cell quantities are accurate only for select cell types and there is a tendency for algorithms to have a good relative fit (R 2 ) but a poor absolute fit (normalized mean squared error; NMSE), which suggests systemic biases exist. Nonetheless, using cell fraction estimates to adjust gene expression data, we show that genes associated with influenza virus replication and increased infection pathology are more likely to be identified as significant than when applying traditional statistical tests.

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