Project description:A common hallmark of neoplastic cells is abnormal acquisition of CpG island (CGI) methylation and the silencing of associated gene promoters. To determine the extent and distribution of CGI methylation in colorectal cancer, we solexa sequenced MBD affinity purified DNA prepared from five colorectal tumours and matched colon mucosa from the same individuals.
Project description:A common hallmark of neoplastic cells is abnormal acquisition of CpG island (CGI) methylation and the silencing of associated gene promoters. To determine the extent and distribution of CGI methylation in colorectal cancer, we solexa sequenced MBD affinity purified DNA prepared from five colorectal tumours and matched colon mucosa from the same individuals.
Project description:We report the application of single molecule-based sequencing technology in combination with CXXC affinity purifcation (CAP-seq), MBD affinity purification (MAP-seq) and chromatin immunoprecipitation (ChIP-seq) to generate reciprocal methylation and chromatin modifcation maps in human and mouse. We find that contrary to sequence based prediction methods that humans and mice possess highly equivalent compliments of CpG islands (CGIs). The majority of these CGIs are positive for the active histone modification; H3K4me3 in embryonic stem cells (ES cells) the magnitude of which is correlated with the local density of non-methylated CpG. Approximately half of the human and mouse CGIs are distal to annotated gene promoters, yet more than 40% identify unanticipated transcription start sites as defined by RNA polymerase occupancy and published RNA mapping data. These orphans CGIs preferentially acquire DNA methylation in somatic cells, and this corresponds with a loss of H3K4me3 and RNA polymerase II at these sites. Conversely abnormal CGI methylation found in colorectal tumours showed a distinct distribution relative to that found in normal somatic tissues displaying preferential association with loci marked by H3K27me3 in human ES cells. This study provides a comprehensive functional assessment of CGIs in normal and diseased tissues. Examination of CGI methylation status in human and mouse primary tissues.
Project description:Genome-wide DNA methylation of colorectal cancer patients with lymph node metastases showed global loss of DNA methylation in CG-poor, non-CpG island (CGI) regions. Overall CGI methylation was increased in tumour samples. Differential methylation analysis of CGIs identified 60 putative biomarkers, with >20% increase in DNA methylation in both primary tumour and metastasis samples compared to normal adjacent tissue.
Project description:To identify a panel of m/z markers for the early detection of colorectal cancer (CRC). Identication of a molecular pattern that can distinguish the primary tumours of colorectal cancer with lymph node metastasis compared to those without. Using MALDI MSI data,we developed and validated a machine learning model that can be used for early screening of CRC. Our model yields high sensitivity and specicity in distinguishing normal tissue from the cancerous. Model described here, can be a used in clinical labs for early diagnosis of colorectal cancer.
Project description:Aim is to identify a panel of m/z markers for the early detection of colorectal cancer (CRC). Identification of a molecular pattern that can distinguish the primary tumours of colorectal cancer with lymph node metastasis compared to those without. Materials and Methods: Using MALDI MSI data, we developed and validated a machine learning model that can be used for early screening of CRC. Our model yields high sensitivity and specificity in distinguishing normal tissue from the cancerous. Model described here, can be a used in clinical labs for early diagnosis of colorectal cancer
Project description:Aim is to identify a panel of m/z markers for the early detection of colorectal cancer (CRC). Identification of a molecular pattern that can distin- guish the primary tumours of colorectal cancer with lymph node metastasis compared to those without. Materials and Methods: Using MALDI MSI data, we developed and validated a machine learning model that can be used for early screening of CRC. Results: Our model yields high sensitivity and speci- ficity in distinguishing normal tissue from the cancerous. Model described here, can be a used in clinical labs for early diagnosis of colorectal cancer
Project description:We explored the differential methylation patterns found in cfDNA between no neoplasia (NN; individuals with no colorectal findings, benign pathologies and non-advanced adenomas) and patients with advanced neoplasia (AN; advanced adenomas and colorectal cancer) using pooled samples, for the discovery of non-invasive methylation biomarkers for CRC screening. cfDNA was extracted from serum samples and methylation measurements were assessed with the Infinium MethylationEPIC BeadChip. Data was mainly preprocessed and analyzed with R/Bioconductor packages.
Project description:We report the application of single molecule-based sequencing technology in combination with CXXC affinity purifcation (CAP-seq), MBD affinity purification (MAP-seq) and chromatin immunoprecipitation (ChIP-seq) to generate reciprocal methylation and chromatin modifcation maps in human and mouse. We find that contrary to sequence based prediction methods that humans and mice possess highly equivalent compliments of CpG islands (CGIs). The majority of these CGIs are positive for the active histone modification; H3K4me3 in embryonic stem cells (ES cells) the magnitude of which is correlated with the local density of non-methylated CpG. Approximately half of the human and mouse CGIs are distal to annotated gene promoters, yet more than 40% identify unanticipated transcription start sites as defined by RNA polymerase occupancy and published RNA mapping data. These orphans CGIs preferentially acquire DNA methylation in somatic cells, and this corresponds with a loss of H3K4me3 and RNA polymerase II at these sites. Conversely abnormal CGI methylation found in colorectal tumours showed a distinct distribution relative to that found in normal somatic tissues displaying preferential association with loci marked by H3K27me3 in human ES cells. This study provides a comprehensive functional assessment of CGIs in normal and diseased tissues.
Project description:Whole-genome screening of CpG Island methylation status by array-based profiling of absolute methylation status (array-PAMS). Methylation-specifically digested DNA (Cy3) was hybridized against methylation-sensitively digested DNA (Cy5) from the same sample. CGI methylation in 20 pediatric medulloblastomas (M) and normal cerebellum (Cb, pool of five unaffected donors, age 25â33 years)