Search results for "High-throughput"
showing 10 items of 292 documents
Application of patient-derived liver cancer cells for phenotypic characterization and therapeutic target identification.
2018
Primary liver cancer (PLC) ranks among the most lethal solid cancers worldwide due to lack of effective biomarkers for early detection and limited treatment options in advanced stages. Development of primary culture models that closely recapitulate phenotypic and molecular diversities of PLC is urgently needed to improve the patient outcome. Long-term cultures of 7 primary liver cancer cell lines of hepatocellular and cholangiocellular origin were established using defined culture conditions. Morphological and histological characteristics of obtained cell lines and xenograft tumors were analyzed and compared to original tumors. Time course analyses of transcriptomic and genomic changes were…
Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor.
2014
Small cell lung cancer (SCLC) is an aggressive disease with high mortality, and the identification of effective pharmacological strategies to target SCLC biology represents an urgent need. Using a high-throughput cellular screen of a diverse chemical library, we observe that SCLC is sensitive to transcription-targeting drugs, in particular to THZ1, a recently identified covalent inhibitor of cyclin-dependent kinase 7. We find that expression of super-enhancer-associated transcription factor genes, including MYC family proto-oncogenes and neuroendocrine lineage-specific factors, is highly vulnerability to THZ1 treatment. We propose that downregulation of these transcription factors contribut…
Single-Cell Analysis of RNA Virus Infection Identifies Multiple Genetically Diverse Viral Genomes within Single Infectious Units
2015
Summary Genetic diversity enables a virus to colonize novel hosts, evade immunity, and evolve drug resistance. However, viral diversity is typically assessed at the population level. Given the existence of cell-to-cell variation, it is critical to understand viral genetic structure at the single-cell level. By combining single-cell isolation with ultra-deep sequencing, we characterized the genetic structure and diversity of a RNA virus shortly after single-cell bottlenecks. Full-length sequences from 881 viral plaques derived from 90 individual cells reveal that sequence variants pre-existing in different viral genomes can be co-transmitted within the same infectious unit to individual cell…
Identification of new P-glycoprotein inhibitors derived from cardiotonic steroids
2014
P-glycoprotein (ABCB1, MDR1) is capable of extruding chemotherapeutics outside the cell and its overexpression in certain cancer cells may cause failure of chemotherapy. Many attempts were carried out to identify potent inhibitors of this transporter and numerous compounds were shown to exert inhibitory effects in vitro, but so far none were able to make their way to the clinic due to serious complications. Natural compounds represent a great source of therapeutics, which are believed to be safe and effective. Therefore, we have screened a large library of naturally occurring cardiotonic steroids and their derivatives using high throughput flow cytometry. We were able to identify six compou…
Mating-induced differential peptidomics of neuropeptides and protein hormones in Agrotis ipsilon moths
2018
International audience; In many insects, mating induces drastic changes in male and female responses to sex pheromones or host-plant odors. In the male moth Agrotis ipsilon, mating induces a transient inhibition of behavioral and neuronal responses to the female sex pheromone. As neuropeptides and peptide hormones regulate most behavioral processes, we hypothesize that they could be involved in this mating-dependent olfactory plasticity. Here we used next-generation RNA sequencing and a combination of liquid chromatography, matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, and direct tissue profiling to analyze the transcriptome and peptidome of diffe…
Solution Processed Micro- and Nano-Bioarrays for Multiplexed Biosensing
2012
This Feature article reports on solution dispensing methodologies which enable the realization of multiplexed arrays at the micro- and nanoscale for relevant biosensing applications such as drug screening or cellular chips.
Molecular evolution and complete genome sequences in forensic analysis: Neisseria gonorrhoeae in a transmission case
2019
Molecular epidemiology and phylogenetic analyses are frequently used in the investigation of viral transmission cases in forensic contexts. Here, we present the methods and results of the analysis of a bacterial transmission in an alleged child abuse case using complete genome sequences obtained by high-throughput sequencing (HTS) methods.
Transcriptome profiling of citrus fruit response to huanglongbing disease.
2010
Huanglongbing (HLB) or "citrus greening" is the most destructive citrus disease worldwide. In this work, we studied host responses of citrus to infection with Candidatus Liberibacter asiaticus (CaLas) using next-generation sequencing technologies. A deep mRNA profile was obtained from peel of healthy and HLB- affected fruit. It was followed by pathway and protein-protein network analysis and quantitative real time PCR analysis of highly regulated genes. We identified differentially regulated pathways and constructed networks that provide a deep insight into the metabolism of affected fruit. Data mining revealed that HLB enhanced transcription of genes involved in the light reactions of phot…
Parallelizing Epistasis Detection in GWAS on FPGA and GPU-Accelerated Computing Systems
2015
This is a post-peer-review, pre-copyedit version of an article published in IEEE - ACM Transactions on Computational Biology and Bioinformatics. The final authenticated version is available online at: http://dx.doi.org/10.1109/TCBB.2015.2389958 [Abstract] High-throughput genotyping technologies (such as SNP-arrays) allow the rapid collection of up to a few million genetic markers of an individual. Detecting epistasis (based on 2-SNP interactions) in Genome-Wide Association Studies is an important but time consuming operation since statistical computations have to be performed for each pair of measured markers. Computational methods to detect epistasis therefore suffer from prohibitively lon…
PVAmpliconFinder: a workflow for the identification of human papillomaviruses from high-throughput amplicon sequencing
2019
Abstract Background The detection of known human papillomaviruses (PVs) from targeted wet-lab approaches has traditionally used PCR-based methods coupled with Sanger sequencing. With the introduction of next-generation sequencing (NGS), these approaches can be revisited to integrate the sequencing power of NGS. Although computational tools have been developed for metagenomic approaches to search for known or novel viruses in NGS data, no appropriate tool is available for the classification and identification of novel viral sequences from data produced by amplicon-based methods. Results We have developed PVAmpliconFinder, a data analysis workflow designed to rapidly identify and classify kno…