EXPERIMENT_TITLE: GSM3560407: HiC_wbc_rep1; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: WBCs are freshly isolated from whole blood, purified neutrophils are obtained frozen from a commercial source (Astarte Biologics Inc) and then thawed Hi-C library preparation on white blood cells and neutrophils was performed using the Arima-HiC kit (Arima Genomics, Inc.; Cat # A510008), according to the manufacturer's protocols. Briefly, WBCs (freshly isolated from whole blood) or purified neutrophils (obtained frozen from a commercial source and then thawed) were crosslinked using formaldehyde. Crosslinked cells were then subject to the Arima-HiC protocol, which utilizes multiple restriction enzymes to digest chromatin. Arima-HiC sequencing libraries were prepared by first shearing purified proximally-ligated DNA and then size-selecting 200-600 bp DNA fragments using SPRI beads. The size-selected fragments were then enriched using Enrichment Beads (provided in Arima-HiC kit), and then converted into Illumina-compatible sequencing libraries with TruSeq adapters using the KAPA Hyper Prep kit. The purified, PCR-amplified DNA underwent standard QC (qPCR and Bioanalyzer) and was sequenced with unique dual indexes on the Illumina HiSeq X (WBC) or NovaSeq 6000 (neutrophils) Sequencing System at 2x151 base pairs.
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Three-dimensional chromatin organization varies across different cell types and is essential for gene regulation. However, current technologies are unable to assess in vivo genome-wide chromatin organization non-invasively. Here, we showed that long-range correlations in the fragment length of cell-free DNA (cfDNA) estimated from whole-genome sequencing recapitulate three-dimensional chromatin organization. The inferred organization is highly concordant with that measured by Hi-C in white blood cells from healthy donors, and is not explained by technical bias or sequence composition. Furthermore, the inferred organization reflects the differing genome organizations in the various cell types contributing to cfDNA, allowing quantification of cfDNA tissue-of-origin that is concordant with previous methods, but at much lower required DNA input. Our results, demonstrated in cfDNA from healthy individuals and cancer patients, may enable noninvasive monitoring of in vivo genome organization and accurate quantification of cell death in different clinical conditions. Overall design: Compare two-dimensional fragmentation pattern in cell free DNA with Hi-C at white blood cell and then deconvolute the signals to reference cell types
SAMPLE_TITLE: HiC_wbc_rep1
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "white blood cells"}, {"TAG": "cell type", "VALUE": "primary cell"}, {"TAG": "restriction enzyme", "VALUE": "Arima (multi-enzyme)"}]
Pool_Member_@attributes_sample_title: HiC_wbc_rep1
RUN_SET_RUN_Pool_Member_@attributes_sample_title: HiC_wbc_rep1
RUN_SET_RUN_SRAFiles_SRAFile: [{"Alternatives": [null, null, null], "@attributes": {"cluster": "public", "filename": "SRR8435322.sralite", "url": "https://sra-downloadb.be-md.ncbi.nlm.nih.gov/sos5/sra-pub-zq-14/SRR008/435/SRR8435322.sralite.1", "size": "37533103988", "date": "2021-06-15 07:27:17", "md5": "076fd94b028ffb90b1b096ed3e9ebba8", "version": "1", "semantic_name": "SRA Lite", "supertype": "Primary ETL", "sratoolkit": "1"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "SRR8435322", "url": "https://sra-pub-run-odp.s3.amazonaws.com/sra/SRR8435322/SRR8435322", "size": "59302451964", "date": "2019-01-11 22:20:38", "md5": "fdc377cb05a9bc0807466143981f62c7", "version": "1", "semantic_name": "SRA Normalized", "supertype": "Primary ETL", "sratoolkit": "1"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "BY_rp1_USPD16080274_H7WV5ALXX_L7_2.fq.gz", "size": "45701254272", "date": "2020-02-06 15:23:33", "md5": "5287ab2f1df51aebb904c80743fb6da9", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "BY_rp1_USPD16080274_H7WV5ALXX_L7_1.fq.gz", "size": "41016364354", "date": "2020-02-06 17:40:08", "md5": "d19fdfcaf8f870d8fd6a5b8442e1ef69", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}]