Project description:Primary objectives: The primary objective is to investigate circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Primary endpoints: circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Project description:Gastric cancer is one of the leading causes of cancer mortality worldwide, and peritoneal metastasis is a hallmark of incurable advanced gastric cancer. The identification of molecular vulnerability for such conditions is imperative to improve the prognosis of gastric cancer. Here, we comprehensively analysed cancer cells purified from malignant ascitic fluid samples and their corresponding cell lines from 98 patients, through whole-genome sequencing, whole transcriptome sequencing, methylation analyses, and genome-wide enhancer analyses.
Project description:In order to more accurately discover the cause of drug resistance in tumor treatment, and to provide a new basis for precise treatment.
Therefore, based on the umbrella theory of precision medicine, we carried out this single-center, prospective, and observational study to include patients with liver metastases from colorectal cancer. By combining genome, transcriptome, and proteomic sequencing data, we established a basis for colorectal cancer liver Transfer the multi-omics data of the sample, describe the reason for the resistance of the first-line treatment, and search for new therapeutic targets.
Project description:Gastric cancer is one of the leading causes of cancer mortality worldwide, and peritoneal metastasis is a hallmark of incurable advanced gastric cancer. The identification of molecular vulnerability for such conditions is imperative to improve the prognosis of gastric cancer. Here, we comprehensively analysed cancer cells purified from malignant ascitic fluid samples and their corresponding cell lines from 98 patients, through whole-genome sequencing, whole transcriptome sequencing, methylation analyses, and genome-wide enhancer analyses.
Project description:Gastric cancer is one of the leading causes of cancer mortality worldwide, and peritoneal metastasis is a hallmark of incurable advanced gastric cancer. The identification of molecular vulnerability for such conditions is imperative to improve the prognosis of gastric cancer. Here, we comprehensively analysed cancer cells purified from malignant ascitic fluid samples and their corresponding cell lines from 98 patients, through whole-genome sequencing, whole transcriptome sequencing, methylation analyses, and genome-wide enhancer analyses.
Project description:The Australian Acute Care Genomics program provides ultra-rapid diagnostic testing to critically ill infants and children with suspected genetic conditions. Over two years, we performed whole genome sequencing (WGS) in 290 families, with average time to result of 2.9 days, and diagnostic yield of 47%. We performed additional bioinformatic analyses and transcriptome sequencing in all patients who remained undiagnosed. Long-read sequencing and functional assays, ranging from clinically accredited enzyme analysis to bespoke quantitative proteomics, were deployed in selected cases. This resulted in an additional 19 diagnoses, and an overall diagnostic yield of 54%. Diagnostic variants ranged from structural chromosomal abnormalities through to an intronic retrotransposon, disrupting splicing. Critical care management changed in 120 diagnosed patients (77%). Results informed precision treatments; surgical and transplant decisions; and palliation in 94 (60%). We propose that integration of multi-omic approaches into mainstream diagnostic practice is necessary to realise the full potential of genomic testing.
Project description:The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC) is not well understood. Comprehensive molecular analyses were performed including high-pass whole-genome sequencing, targeted deep DNA sequencing, RNA sequencing, reverse-phase protein arrays, mass spectrometry-based proteomics and phosphoproteomics, and immune profiling on primary and metastatic sites from highly clinically annotated HGSC samples. Samples were obtained pre-treatment based on a laparoscopic triage algorithm from patients who underwent R0 tumor debulking or received neoadjuvant chemotherapy (NACT) with excellent or poor response.
Project description:Whole genome shotgun bisulfite sequencing, small RNA sequencing and transcriptome sequencing of wildtype Arabidopsis plants (Col-0), and met1, drm1 drm2 cmt3, and ros1 dml2 dml3 null mutants using the Illumina Genetic Analyzer. A comparison was performed with regions of the genome containing cytosine DNA methylation identified by methylcytosine immunoprecipitation and whole-genome oligonucleotide tiling microarrays, for wildtype Col-0. Understanding the epigenetic regulatory mechanisms that mediate control of transcription at multiple levels is critical to understanding how plants develop and respond to their environment. We combined next-generation sequencing by synthesis (SBS) technology with novel methods for direct sequencing of the entire cytosine methylome (methylC-seq), transcriptome (RNA-seq), and the small RNA component of the transcriptome (smRNA-seq) to create a set of highly integrated epigenome maps for Arabidopsis thaliana, in conjunction with a set of informative mutants defective in DNA methyltransferase and DNA demethylase activity. At single-base resolution we discovered extensive, previously undetected, DNA methylation, identified the context and level of methylation at each site, and found that local composition has effects upon DNA methylation state. Deep sequencing of the smRNAome exposed a direct relationship between the location and abundance of smRNAs and DNA methylation, perturbation of smRNA biogenesis upon loss of CpG DNA methylation, and a tendency for smRNAs to direct strand-specific DNA methylation in the region of RNA-DNA homology. Finally, strand-specific RNA-seq revealed changes in the transcript abundance of hundreds of genes upon alteration of the DNA methylation state, and enabled the identification of numerous previously unidentified genes regulated by DNA methylation. Keywords: Whole genome shotgun bisulfite sequencing, small RNA sequencing, transcriptome sequencing, methylcytosine immunoprecipitation, whole-genome oligonucleotide tiling microarrays Whole genome shotgun bisulfite sequencing, small RNA sequencing and transcriptome sequencing of wildtype Arabidopsis plants (Col-0), and met1, drm1 drm2 cmt3, and ros1 dml2 dml3 null mutants using the Illumina Genetic Analyzer. A comparison was performed with regions of the genome containing cytosine DNA methylation identified by methylcytosine immunoprecipitation and whole-genome oligonucleotide tiling microarrays, for wildtype Col-0.
Project description:In this study, we have applied the top-down approach to reduce the genome of B. subtilis in order to obtain minimal strains with robust growth on complex medium at 37°C. For this purpose, we have evaluated the function of each gene of the B. subtilis genome and identified essential, important and dispensable genomic regions. Using an efficient markerless and scarless deletion method and a system allowing induction of genetic competence in the complete cell population, we have constructed two genome-reduced strains lacking about 36% of dispensable genetic information. Multi-omics analyses with the genome-reduced strains revealed substantial changes in the transcriptome, the proteome and in the metabolome. The massive reorganization of metabolism in the two genome-reduced strains can be explained by the underlying genotypes that were determined by genome re-sequencing. Moreover, the transcriptome and proteome analyses uncovered novel dispensable genomic regions that can be removed to further streamline the B. subtilis genome. In conclusion, both minimal strains show interesting metabolic features and they serve as excellent starting points to generate an ultimate reduced-genome B. subtilis cell containing only genes required for robust growth on complex medium.