Luo, F. — Page 4 | bioRxiv Science

bioRxiv2017

DNA 5-Hydroxymethylcytosines from Cell-free Circulating DNA as Diagnostic Biomarkers for Human Cancers

DNA modifications such as 5-methylcytosines (5mC) and 5-hydroxymethylcytosines (5hmC) are epigenetic marks known to affect global gene expression in mammals(1, 2). Given their prevalence in the human genome, close correlation with gene expression, and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology(3), we report here genome-wide 5hmC profiling in circulating cell-free DNA (cfDNA) and in genomic DNA of paired tumor/adjacent tissues collected from a cohort of 90 healthy individuals and 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver, or thyroid cancer. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures in cfDNA were identified with specificity for different cancers. 5hmC-based biomarkers of circulating cfDNA demonstrated highly accurate predictive value for patients with colorectal and gastric cancers versus healthy controls, superior to conventional biomarkers, and comparable to 5hmC biomarkers from tissue biopsies. This new strategy could lead to the development of effective blood-based, minimally-invasive cancer diagnosis and prognosis approaches.

cancer biology↗

bioRxiv2016

MECAT: an ultra-fast mapping, error correction and de novo assembly tool for single-molecule sequencing reads

The high computational cost of current assembly methods for the long, noisy single molecular sequencing (SMS) reads has prevented them from assembling large genomes. We introduce an ultra-fast alignment method based on a novel global alignment score. For large human SMS data, our method is 7X faster than MHAP for pairwise alignment and 15X faster than BLASR for reference mapping. We develop a Mapping, Error Correction and de novo Assembly Tool (MECAT) by integrating our new alignment and error correction methods, with the Celera Assembler. MECAT is capable of producing high quality de novo assembly of large genome from SMS reads with low computational cost. MECAT produces reference-quality assemblies of Saccharomyces cerevisiae, Arabidopsis thaliana, Drosophila melanogaster and reconstructs the human CHM1 genome with 15% longer NG50 in only 7600 CPU core hours using 54X SMS reads and a Chinese Han genome in 19200 CPU core hours using 102X SMS reads.

bioinformatics↗