Project description:Chronic myeloid leukemia (CML) epitomizes successful targeted therapy, with 86% of patients in the chronic phase treated with tyrosine kinase inhibitors (TKIs) attaining remission. However, resistance to TKIs occurs during treatment, and patients with resistance to TKIs progress to the acute phase called Blast Crisis (BC), wherein the survival is restricted to 7-11 months. About 80 % of patients in BC are unresponsive to TKIs. This issue can be addressed by identifying a molecular signature which can predict resistance in CML-CP prior to treatment as well as by delineating the molecular mechanism underlying resistance. Herein, we report genomic analysis of CML patients and imatinib-resistant K562 cell line to achieve the same. WGS was performed on imatinib-sensitive and -resistant K562 cells. Library preparation was done by 30x WGS KAPA PCR-Free v2.1 kit, and Illumina HiSeq X sequencer was used for 2 x 150 bp paired-end sequencing. Our study identified accumulation of aberrations on chromosomes 1, 3, 7, 16 and 22 as predictive of occurrence of resistance. Further, recurrent amplification in chromosomal region 8q11.2-12.1 was detected in highly resistant K562 cells as well as CML patients. The genes present in this region were analyzed to understand molecular mechanism of imatinib resistance.
Project description:Chromosomal copy number variations (CNV) have been associated with various neurological and developmental disorders and chromosomal microarray (CMA) is a method of choice to diagnose Copy Number Gain/Loss syndromes. Recently, next-generation sequencing (NGS)-based low-coverage whole genome sequencing (LC-WGS) has been applied to detect Copy Number Gain/Loss syndromes. This dataset is intended to be used as a “Golden standard data set” for development of LC-WGS analysis method. It consists of patients (n=63) who have a mental delay and/or physical disability phenotype and normal (n=20) phenotype.
Project description:This dataset holds three runs of our new Atrandi-SPC based single-cell WGS protocol, one for each lysis protocol (R1-R3 in the study)
Project description:Whole genome sequencing (WGS) of tongue cancer samples and cell line was performed to identify the fusion gene translocation breakpoint. WGS raw data was aligned to human reference genome (GRCh38.p12) using BWA-MEM (v0.7.17). The BAM files generated were further analysed using SvABA (v1.1.3) tool to identify translocation breakpoints. The translocation breakpoints were annotated using custom scripts, using the reference GENCODE GTF (v30). The fusion breakpoints identified in the SvABA analysis were additionally confirmed using MANTA tool (v1.6.0).
Project description:The fallopian tube (FT) has been proposed as a potential site of origin for high-grade serous ovarian cancer (HGSOC), supporting investigation of genomic alterations across matched tissues. This dataset includes whole-genome sequencing (WGS) and DigiPico data from matched samples, including peripheral blood mononuclear cells (PBMCs), fallopian tube tissue, and tumor tissue from HGSOC patients. The data support analysis of germline and somatic variants, copy number alterations (CNAs), and neoantigen prediction across matched sample types. This submission contains the WGS data DigiPico data associated with this study.
Project description:CTCF ChIP-seq of 39 primary samples derived from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011059 (dataset).
Project description:The expression profile and sequence variants of 476 early stage urothelial carcinoma were studied using whole transcriptome sequencing. RNA-Seq libraries were prepared by Ribo-Zero treatment of total-RNA (to reduce the rRNA content) followed by library preparation using ScriptSeq. RNA-Seq libraries were paired-end sequenced (2x 101 bp) on Illumina HiSeq 2000 and the resulting fastq files were processed using tools from the Genome Analysis Toolkit (GATK and from the Tuxedo suite. Access to the sequence data (bam and vcf files), containing person identifying information, needs signature on a controlled access form, and can be accessed at The European Genome-phenome Archive (EGA) using the study ID EGAS00001001236 following request. An expression matrix of FPKM values are available without restriction at ArrayExpress.
Project description:H3K27ac ChIP-seq of 79 primary samples derived from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). In addition, 4 samples derived from CD34+ cord blood cells of healthy donors were included. Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011060 (dataset).
Project description:Chronic myeloid leukemia (CML) is a biphasic clonal hematopoietic stem cell disorder driven by the Philadelphia chromosome (Ph)-encoded BCR::ABL1 oncogene. The blast phase (BP) in CML progressed from indolent chronic phase (CP), usually has a dismal outcome. Single-cell RNA sequencing (scRNA-seq) have identified the pretreatment features linked to therapy resistance and disease progression. We performed the scRNA-seq on bone marrow cells derived from paired CML-CP and CML-BLBC samples, and found that CD24 displayed a striking upregulation in CML-BLBC samples when compared with both the CML-CP and Ph+ B-ALL samples, suggesting the potential as a target in the future therapy of patients with CML-BLBC. Therefore, we profiled the BM samples from patients with CML-CP (n = 16), CML-BLBC (n = 8), and de novo Ph+ B-ALL (n = 13) using bulk RNA sequencing to validate the upregulated expressio of CD24 in patients with CML-BLBC.