bioRxiv ScienceSearch

Biology subjects

Qing, Y.

Publications and source records attributed to Qing, Y..

2 recordsLinked to original sources

SCYN: Single cell CNV profiling method using dynamic programming

Copy number variation is crucial in deciphering the mechanism and cure of complex disorders and cancers. The recent advancement of scDNA sequencing technology sheds light upon addressing intratumor heterogeneity, detecting rare subclones, and reconstructing tumor evolution lineages at single-cell resolution. Nevertheless, the current circular binary segmentation based approach proves to fail to efficiently and effectively identify copy number shifts on some exceptional trails. Here, we propose SCYN, a CNV segmentation method powered with dynamic programming. SCYN resolves the precise segmentation on two in silico datasets. Then we verified SCYN manifested accurate copy number inferring on triple negative breast cancer scDNA data, with array comparative genomic hybridization results of purified bulk samples as ground truth validation. We tested SCYN on two datasets of the newly emerged 10x Genomics CNV solution. SCYN successfully recognizes gastric cancer cells from 1% and 10% spike-ins 10x datasets. Moreover, SCYN is about 150 times faster than state of the art tool when dealing with the datasets of approximately 2000 cells. SCYN robustly and efficiently detects segmentations and infers copy number profiles on single cell DNA sequencing data. It serves to reveal the tumor intra-heterogeneity. The source code of SCYN can be accessed in https://github.com/xikanfeng2/SCYN. The visualization tools are hosted on https://sc.deepomics.org/.

bioinformatics

Direct detection of molecular intermediates from first-passage times

All natural phenomena are governed by energy landscapes. However, the direct measurement of this fundamental quantity remains challenging, particularly in complex systems involving intermediate states. Here, we uncover key details of the energy landscapes that underpin a range of experimental systems through quantitative analysis of first-passage time distributions. By combined study of colloidal dynamics in confinement, transport through a biological pore and the folding kinetics of DNA hairpins, we demonstrate conclusively how a short-time, power-law regime of the first-passage time distribution universally reflects the number of intermediate states associated with each process, irrespective of the lengthscales, timescales or interactions in the system. We thereby establish a powerful method for investigating the underlying mechanisms of complex molecular processes.

biophysics