Project description:The objective of this study was to measure copy number alterations in a panel of 15 CRC cell lines and relate them to treatment sensitivity. Assessment of copy number variations in a panel of 15 colorectal cancer cell lines
Project description:Mutations in PfCRT confer chloroquine (CQ) resistance in P. falciparum. Point mutations in the homolog of the mammalian multidrug resistance gene (pfmdr1) can also modulate the levels of CQ response. However, parasites with the same pfcrt and pfmdr1 alleles exhibit a wide range of drug sensitivity, suggesting that additional genes contribute to levels of CQ resistance (CQR). We used 3 isogenic lines which have different drug resistance profiles corresponding to unique mutations in the pfcrt gene (106/1K76, 106/176I, and 106/76I-352K) to study changes in gene expression with and without CQ and genomic variations, i.e. copy number (CN) changes. RNA transcription levels from 45 genes were significantly altered in one or both mutants relative to the parent line. Of particular interest are genes encoding proteins involved in transport and/or regulation of cytoplasmic or compartmental pH, e.g. the V-type H+ pumping pyrophosphatase 2, Ca2+/H+ antiporter VCX1 and copy number changes in pfmdr1. A series of deletion (including 15 genes) also occurred at the beginning of chromosome 10. Keywords: low-dose 3h Chloroquine response, copy number variation
Project description:Analysis of DNA copy number variations in two DDLS tumor-derived cell lines DDLS8817 and LPS141 growing in culture in basal conditions The goal of this DNA copy number analysis was to determine if genes used in signaling network modeling in DDLS were amplified or deleted
Project description:Leishmaniasis is a neglected tropical disease affecting millions of people worldwide. Emerging drug resistance of Leishmania species poses threaten to the effective control and elimination of this neglected tropical disease. Here we conducted whole genome resequencing, proteome profiling, and comparative analyses of a drug-resistant clinical isolate and two drug-susceptible strains of Leishmania donovani to explore genetic features that might contribute to the establishment of drug resistance in this parasite. By comparative genomic analysis, exclusive variations were identified in the drug-resistant isolate of L. donovani, including 86 copy number variations, 271 frameshift mutations in protein-coding genes and two site mutations in non-coding genes. Comparative proteomic analysis indicated significant differences in protein expression between resistant and susceptible strains of L. donovani, including 69 exclusive detected molecules and 84 consistent down-/up-regulations in the former. Integrating the genomic mutations and proteomic specificities linked nine of the genomic mutations (gene duplication, insertion and deletion) to significantly altered protein expression changes in the drug-resistant clinical isolate. These genetic features were inferred to be associated with nucleotide-binding and fatty acid metabolism (biosynthesis and degradation), which might contribute to fitness-gains allowing for the drug-resistant phenotype of L. donovani. This comparative and integrative work provided deep insights into the molecular basis underlying resistance establishment, suggesting new aspects to be investigated for novel intervention strategies against L. donovani and related species.
Project description:Somatic DNA copy number variations (CNVs) are prevalent in cancer and can drive cancer progression albeit with often uncharacterized roles in altering cell signaling states. We developed a computational approach to predict regulators of signaling from the integrative analysis of genomic and proteomic pan-cancer datasets. Among the predictions, we identified ARHGEF17 to be a regulator of hippo-signaling and performed (phospho)proteomics analysis to test these predictions.
Project description:The aim of this study is to determine copy number variations in the multiple myeloma patients, which were positive for BCL1/JH t(11;14)(q13;q32) translocation. Identification of common chromosomal aberrations representing the t(11;14)(q13;q32) subtype is possible by comparing the microarray data across all the samples under studied.
