Project description:In this experiment we examined the genes regulated by PAX8 knockdown in four renal cell carcinoma models. Four different cell lines bearing a validated doxycycline (DOX) inducible shRNA against PAX8 were treated with DOX for 96 hours and their gene expression profile analyzed by RNA-seq.
Project description:Mathematical modeling of regulatory T cell effects on renal cell carcinoma treatment
Lisette dePillis 1, , Trevor Caldwell 2, , Elizabeth Sarapata 2, and Heather Williams 2,
1.
Department of Mathematics, Harvey Mudd College, Claremont, CA 91711
2.
Harvey Mudd College, Claremont, CA 91711, United States, United States, United States
Abstract
We present a mathematical model to study the effects of the regulatory T cells (Treg) on Renal Cell Carcinoma (RCC) treatment with sunitinib. The drug sunitinib inhibits the natural self-regulation of the immune system, allowing the effector components of the immune system to function for longer periods of time. This mathematical model builds upon our non-linear ODE model by de Pillis et al. (2009) [13] to incorporate sunitinib treatment, regulatory T cell dynamics, and RCC-specific parameters. The model also elucidates the roles of certain RCC-specific parameters in determining key differences between in silico patients whose immune profiles allowed them to respond well to sunitinib treatment, and those whose profiles did not.
Simulations from our model are able to produce results that reflect clinical outcomes to sunitinib treatment such as: (1) sunitinib treatments following standard protocols led to improved tumor control (over no treatment) in about 40% of patients; (2) sunitinib treatments at double the standard dose led to a greater response rate in about 15% the patient population; (3) simulations of patient response indicated improved responses to sunitinib treatment when the patient's immune strength scaling and the immune system strength coefficients parameters were low, allowing for a slightly stronger natural immune response.
Keywords: Renal cell carcinoma, mathematical modeling., sunitinib, immune system, regulatory T cells.
Project description:Raw data from E-MTAB-1585 was normalized by using reads per million. https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1585/ Strand specific RNA-Seq data E-MTAB-1585 was normalized and subtracted control from knockdown to generate tracks that more clearly displayed the unusual pattern of RNA expression caused by knockdown of 7SK. The following wig files were generated from multiple samples (i.e.raw data files), as indicated in the 'readme.txt' file. 7sk_3p_KD_norm.wig: 7SK 3P Knockdown normalized 7sk_3p_KDF_norm.wig: 7SK 3P Knockdown normalized (Forward) 7sk_3p_KDR_norm.wig: 7SK 3P Knockdown normalized (Reverse) 7sk_5p_KD_norm.wig: 7SK 5P Knockdown normalized 7sk_5p_KDF_norm.wig: 7SK 5P Knockdown normalized (Forward) 7sk_5p_KDR_norm.wig: 7SK 5P Knockdown normalized (Reverse) 7sk_Control_norm.wig: 7SK Control normalized 7sk_ControlF_norm.wig: 7SK Control normalized (Forward) 7sk_ControlR_norm.wig: 7SK Control normalized (Reverse) 7sk_3p_KDF-ControlF.wig: 7SK 3P Knockdown-Control (Forward) 7sk_3p_KDR-ControlR.wig: 7SK 3P Knockdown-Control (Reverse) 7sk_5p_KDF-ControlF.wig: 7SK 5P Knockdown-Control (Forward) 7sk_5p_KDR-ControlR.wig: 7SK 5P Knockdown-Control (Reverse)
Project description:Aberrant DNA methylation is common in cancer. To associate DNA methylation with gene function, we performed RNAseq upon tumor tissue and matched normal tissues of two ccRCC (clear cell renal cell carcinoma) patients. To quantify 5mC and 5hmC level in each CG site at genome-wide level, we performed BS-seq and TAB-seq upon tumor tissue and matched normal tissues of two ccRCC (clear cell renal cell carcinoma) patients, respectively. mRNA profiles of tumor and matched normal tissues from two ccRCC patients were generated by deep sequencing, using Hiseq 2000. Single-nucleotide-resolution, whole-genome, 5mC and 5hmC profiles of tumor and matched normal tissues from two ccRCC (clear cell renal cell carcinoma) patients were generated by deep sequencing, using Hiseq 2000.
Project description:Aberrant DNA methylation is common in cancer. To associate DNA methylation with gene function, we performed RNAseq upon tumor tissue and matched normal tissues of two ccRCC (clear cell renal cell carcinoma) patients. To quantify 5mC and 5hmC level in each CG site at genome-wide level, we performed BS-seq and TAB-seq upon tumor tissue and matched normal tissues of two ccRCC (clear cell renal cell carcinoma) patients, respectively.