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Cancer Genomics Lab at Johns Hopkins

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Dr Shashikant Koul
skoul3@jh.edu

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This DAC controls 17 datasets

Dataset ID	Description	Technology	Samples
EGAD00001001421	Clinical Implications of Genomic Alterations in the Tumour and Circulation of Pancreatic Cancer Patients	Illumina MiSeq	125
EGAD00001003792	The dataset for High Grade Serous Ovarian Carcinomas Originate in the Fallopian Tube includes 46 bam files from next-generation sequencing on the Illumina HiSeq2500. The samples analyzed include multiple lesions from nine patients, five with high grade serous ovarian carcinoma and four who are BRCA-carriers.	Illumina HiSeq 2500	46
EGAD00001004532	In this dataset there are 55 whole genome sequencing samples of epithelial ovarian carcinoma (bam files).	Illumina HiSeq 2500	55
EGAD00001005111	Most patients with late stage high-grade serous ovarian cancer (HGSOC) initially respond to chemotherapy but inevitably relapse and develop resistance, highlighting the need for novel therapies to improve patient outcomes. The MEK/ERK pathway is activated in a large subset of HGSOC, thus making it an attractive therapeutic target. Here, we systematically evaluated the extent of MEK/ERK pathway activation and efficacy of pathway inhibition in a large panel of well-annotated HGSOC patient-derived xenograft (PDX) models. The vast majority of models were nonresponsive to the MEK inhibitor cobimetinib (GDC-0973) despite effective pathway inhibition. Proteomic analyses of adaptive responses to GDC-0973 revealed that GDC-0973 upregulated the pro-apoptotic protein BIM, thus priming the cells for apoptosis regulated by BCL2-family proteins. Indeed, combination of both MEK inhibitor and dual BCL-2/XL inhibitor (ABT-263) significantly reduced cell number, increased cell death and displayed synergy in vitro in most models. In vivo, the GDC-0973 and ABT-263 combination was well tolerated and resulted in greater tumor growth inhibition than single agents. Detailed proteomic and correlation analyses identified two subsets of responsive models – those with high BIM at baseline that was increased with MEK inhibition and those with low basal Bim and high pERK levels. Models with low BIM and low pERK were non-responsive. Our findings demonstrate that combined MEK and BCL-2/XL inhibition has therapeutic activity in HGSOC models and provide a mechanistic rationale for clinical evaluation of this drug combination as well as the assessment of the extent to which BIM and/or pERK levels predict drug combination effectiveness in chemoresistant HGSOC.	Illumina HiSeq 2500 Illumina MiSeq	14
EGAD00001005339	The dataset for Genome-wide cell-free DNA fragmentation in patients with cancer includes 538 bam files from whole genome next-generation sequencing on the Illumina HiSeq2500. The samples analyzed include plasma samples from healthy individuals and patients with cancer.	Illumina HiSeq 2500	537
EGAD00001005750	The dataset for white blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer includes 169 bam files from targeted deep sequencing on the Illumina HiSeq2500. The samples analyzed include genomic DNA from white blood cells and cell-free DNA from longitudinal blood collections of patients with gastric cancer.	Illumina HiSeq 2500	167
EGAD00001007796	The dataset for Detection and characterization of lung cancer using cell-free DNA fragmentomes includes 872 bam files from whole genome next-generation sequencing on the Illumina HiSeq2500. The samples analyzed include plasma samples from healthy individuals and patients with cancer.	Illumina HiSeq 2500	872
EGAD00001010891	The dataset for Single molecule genome-wide mutation profiles of cell-free DNA for non-invasive detection of cancer includes 57 BAM files from whole genome next-generation sequencing on the Illumina HiSeq2500. The samples analyzed include plasma samples from individuals with and without cancer.	Illumina HiSeq 2500	57
EGAD00001010931	The dataset for Detecting Liver Cancer Using Cell-Free DNA Fragmentomes includes 444 BAM files from whole genome next-generation sequencing on the Illumina NovaSeq 6000. The samples analyzed include plasma samples from individuals with and without cancer.	Illumina NovaSeq 6000	444
EGAD00001015538	The dataset for “Validation of cfDNA fragmentome analyses for early detection of liver cancer” includes 380 cram files from whole genome next-generation sequencing on the Illumina NovaSeq 6000 with 10x coverage. The samples analyzed include plasma samples from patients with cancer and liver disease.	Illumina NovaSeq 6000	380
EGAD00001015823	The dataset includes 63 BAM files from Oxford Nanopore PromethION whole-genome sequencing, generated by base calling POD5 files with Dorado (super-accurate, modified base model v5.0.0_5mCG_5hmCG@v3) and aligning reads to the hg19 reference genome.	PromethION	4
EGAD00001016583	This dataset contains 352 cram files from whole genome next-generation sequencing on the Illumina NovaSeq 6000 with 1-2x coverage. The samples analyzed include plasma samples from patients with Alzheimer's Disease (AD), family history of AD, and patients with no neurological deficits.	Illumina NovaSeq 6000	351
EGAD00001016584	This dataset contains 570 cram files from whole genome next-generation sequencing on the Illumina NovaSeq 6000 with 1-2x coverage. The samples analyzed include plasma samples from non-cancer patients from MICA cohort.	Illumina NovaSeq 6000	570
EGAD50000000695	The dataset for “Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers” includes 409 cram files from whole genome next-generation sequencing on the Illumina HiSeq2500. The samples analyzed include plasma samples from healthy individuals and patients with cancer.	Illumina HiSeq 2500	409
EGAD50000000744	The dataset for “Genomic landscapes of endometrioid and mucinous ovarian cancers and morphologically similar tumor types” includes 288 bam files from whole genome, whole exome and targeted next-generation sequencing on the Illumina HiSeq2500 and MiSeq. The samples analyzed include tumor and normal tissue samples from patients with cancer.	Illumina HiSeq 2500	288
EGAD50000001353	The dataset for “Genome-wide analyses of cell-free DNA for therapeutic monitoring of patients with pancreatic cancer” includes 496 cram files from whole genome next-generation sequencing on the Illumina NovaSeq 6000. The samples analyzed include tumor tissue, matched buffy coat and longitudinal plasma samples from individuals with pancreatic cancer.	Illumina NovaSeq 6000	496
EGAD50000001445	The dataset for “Detection of brain cancer using genome-wide cell-free DNA fragmentomes” includes 310 bam files from whole genome next-generation sequencing on the Illumina Novaseq 6000. The dataset analyzed include plasma cfDNA samples from patients with cancer, patients with neurological conditions, and healthy individuals.	Illumina NovaSeq 6000	310