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• Chondrosarcoma_Validation_Study

  Agilent whole exome hybridisation capture was performed on genomic DNA derived from Chondrosarcoma cancer and matched normal DNA from the same patients. Next Generation sequencing performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. Now we aim to re find and validate the findings of those exome libraries using bespoke pulldown methods and sequencing the products.

  Study EGAS00001000181

• Acute_Myeloid_Leukemia_Sequencing

  Genomic libraries (500 bps) will be generated from total genomic DNA derived from 25 acute myeloid leukemia samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.

  Study EGAS00001000209

• Mate-pair sequencing of 12q-amplified osteosarcomas

  Mate-pair sequencing of 12q-amplified osteosarcomas for the detection of structural variants. This was carried out in order to study the structure of the chromosome 12q-amplicons and whether material from other chromosomes is also intertwined and amplified in a bid to further characterise these tumours beyond CDK4 and MDM2 amplification. Mate-pair data was also used to verify gene fusions detected with RNA-seq.

  Study EGAS50000000493

• Targeted sequencing DDR genes in cancer stem cells

  Colorectal cancer stem cells (CSCs) show heterogeneous levels of constitutive replication stress leading distinct dependence on the replication stress response. The aim of the projects was to find genetic, epigenetic, phenotypic factors associated with the resistance of colorectal CSCs to inhibitors of the ATR/CHK1 pathway, which regulates of the replication stress response. Different pairs of colorectal CSCs sensitive and resistant to ATR or CHK1 inhibitors were analyzed

  Study EGAS00001004892

• TP53 variant detection analysis in high grade serous epithelial ovarian cancer

  The aim of this study was to detect in the DNA purified from PAP test samples collected years before the diagnosis of high grade serous epithelial ovarian cancer the presence of the clonal pathogenic TP53 variant identified in the matched primary tumor biopsy. In this specific part of the study, we analyzed FFPE tumor samples to identify clonal pathogenic variants to be tested in matched PAP tests.

  Study EGAS00001004361

• RNAseq Iron-Treated iPSC-derived Microglia

  Iron accumulation in microglia has been observed in Alzheimer’s disease and other neurodegenerative disorders and is thought to contribute to disease progression through various mechanisms including neuroinflammation. To study the interaction between iron accumulation and inflammation, we treated human induced pluripotent stem cell-derived microglia (iPSC-MG) with an increasing concentration of iron, in combination with inflammatory stimuli such as interferon gamma and amyloid β, and performed RNA sequencing.

  Study EGAS00001006112

• Exome and Whole-Genome Sequencing of Central African Hunter-Gatherers and Agriculturalists

  To investigate how human populations have adapted to the equatorial rainforest, we generated 266 high-coverage exomes, analyzed in combination with 300 published exomes, from 14 populations of African rainforest hunter-gatherers and farmers, together with 40 newly-generated, low-coverage genomes. Genome scans for positive selection and signatures of polygenic selection provide evidence for local adaptation of hunter-gatherers to the African rainforest.

  Study EGAS00001003722

• Heterogeneous metabolic signatures are linked to cancer cell differentiation in colorectal cancer

  Colorectal cancer (CRC) is characterized by functional intratumor heterogeneity that shares many similarites with the hierarchical organization of the normal intestinal epithelium. In order to relate transcriptional subtypes to functional tumor cell heterogeneity we applied scRNA-seq to 12 patient-derived CRC spheroid cultures. We identified shared expression programs that relate to intestinal lineages and revealed metabolic signatures that are linked to cancer cell differentiation. In addition, we validated and complemented sequencing results by quantitative microscopy using live-dyes and multiplexed RNA fluorescence in situ hybridization, thereby revealing metabolic compartmentalization and potential cell-cell interactions. Finally, we demonstrate functional differences between metabolically distinct lineage subtypes that might have strong implications for future treatment strategies of CRC.

  Dataset EGAD00001005524

• Adipocytes Regulate Fibroblast Function and Their Loss Contributes to Fibroblast Dysfunction in Inflammatory Diseases

  We profiled live synovial cells from 16 individuals with no diagnosed arthritis using single-cell RNA sequencing. Our study was designed to provide a reference single cell RNA sequencing dataset for researchers interested in studying arthritic synovium, providing sequencing data on healthy synovial cells for comparison to cells from diseased synovial tissues. Synovial tissue was collected post-mortem from three different sources between 2019-2021: the National Disease Research Interchange, a collaboration with Rush University and the Gift of Hope, and the Brigham and Women's Hospital Autopsy Department. To be included in the study, patients had to be between the ages of 18 to 72 and have no diagnosed arthritis or autoimmune diseases. Additionally, this study includes bulk RNA sequencing data of cultured primary synovial fibroblasts isolated from three rheumatoid arthritis patents. Cells were stimulated with either cortisol, fat conditioned media, TGFβ, TNFα, fat conditioned media with mifepristone, TGFβ with fat conditioned media, or TNFα with fat conditioned media. Cells were harvested 4 or 22 hours later and lysates collected for sequencing. Data from this study submitted to the Gene Expression Omnibus (GEO) may be accessed via accession number GSE233504.

  Study phs003304

• Development of cell lines and mouse models of bone and soft tissue sarcoma to establish novel treatment

  Malignant giant-cell tumors are extremely rare bone sarcomas that transform from conventional giant-cell tumors during long periods of treatment. We have applied the culture methods and succeeded in establishing patient-derived organoids (PDO) of rare sarcomas. This study aimed to investigate the genomic characteristics of our established novel organoids from human malignant giant-cell tumors. The developed tumors with xenograft were genomically analyzed to compare their characteristics with those of the original tumors. Genetic changes over time throughout treatment were analyzed, and the genomic status of the established organoid was confirmed. Next generation sequencing revealed that the established organoids lacked the H3-3A G34W mutation. The xenografted organoids of the malignant giant-cell tumor had phenotypes genetically similar to those of the original tumor. The established organoids were confirmed to be derived from human malignant giant-cell tumors. In summary, the present study demonstrated a novel organoid model of a malignant giant-cell tumor that was genetically confirmed to be a malignant transformed tumor. Our organoid model could be used to elucidate the molecular pathogenesis of a malignant giant-cell tumor and develop novel treatment modalities.

  Study JGAS000618