FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA.

Analysis of DNA methylation in cell-free DNA reveals clinically relevant biomarkers but requires specialized protocols such as whole-genome bisulfite sequencing. Meanwhile, millions of cell-free DNA samples are being profiled by whole-genome sequencing. Here, we develop FinaleMe, a non-homogeneous Hidden Markov Model, to predict DNA methylation of cell-free DNA and, therefore, tissues-of-origin, directly from plasma whole-genome sequencing.

NOMe-HiC: joint profiling of genetic variant, DNA methylation, chromatin accessibility, and 3D genome in the same DNA molecule.

Cis-regulatory elements are coordinated to regulate the expression of their targeted genes. However, the joint measurement of cis-regulatory elements' activities and their interactions in spatial proximity is limited by the current sequencing approaches. We describe a method, NOMe-HiC, which simultaneously captures single-nucleotide polymorphisms, DNA methylation, chromatin accessibility (GpC methyltransferase footprints), and chromosome conformation changes from the same DNA molecule, together with the transcriptome, in a single assay.

CRAG: de novo characterization of cell-free DNA fragmentation hotspots in plasma whole-genome sequencing.

The fine-scale cell-free DNA fragmentation patterns in early-stage cancers are poorly understood. We developed a de novo approach to characterize the cell-free DNA fragmentation hotspots from plasma whole-genome sequencing. Hotspots are enriched in open chromatin regions, and, interestingly, 3'end of transposons.

FinaleDB: a browser and database of cell-free DNA fragmentation patterns.

Summary: Circulating cell-free DNA (cfDNA) is a promising biomarker for the diagnosis and prognosis of many diseases, including cancer. The genome-wide non-random fragmentation patterns of cfDNA are associated with the nucleosomal protection, epigenetic environment and gene expression in the cell types that contributed to cfDNA. However, current progress on the development of computational methods and understanding of molecular mechanisms behind cfDNA fragmentation patterns is significantly limited by the controlled-access of cfDNA whole-genome sequencing (WGS) dataset.

Extracellular RNA in a single droplet of human serum reflects physiologic and disease states.

Extracellular RNAs (exRNAs) are present in human serum. It remains unclear to what extent these circulating exRNAs may reflect human physiologic and disease states. Here, we developed SILVER-seq (Small Input Liquid Volume Extracellular RNA Sequencing) to efficiently sequence both integral and fragmented exRNAs from a small droplet (5 μL to 7 μL) of liquid biopsy.

Gemini surfactant-induced DNA condensation into a beadlike structure.

Using a magnetic tweezers (MT) apparatus and an atomic force microscope (AFM), we studied the condensation of DNA induced by the cationic gemini surfactant hexyl-alpha,omega-bisdodecyldimethylammonium bromide (C12 C6 C12 Br2). Stepwise condensation events were found for forces from 0.5 to 4 pN, with a decrease in DNA extension by approximately 100 nm in each condensation event.