Cifello, J. | bioRxiv Science

bioRxiv2023

hipFG: High-throughput harmonization and integration pipeline for functional genomics data

SummaryPreparing functional genomic (FG) data with diverse assay types and file formats for integration into analysis workflows that interpret genome-wide association and other studies is a significant and time-consuming challenge. Here we introduce hipFG, an automatically customized pipeline for efficient and scalable normalization of heterogenous FG data collections into standardized, indexed, rapidly searchable analysis-ready datasets while accounting for FG datatypes (e.g., chromatin interactions, genomic intervals, quantitative trait loci). Availability and ImplementationhipFG is freely available at https://bitbucket.org/wanglab-upenn/hipFG. Docker container is available at https://hub.docker.com/r/wanglab/hipfg. Contactlswang@pennmedicine.upenn.edu Supplementary informationSupplementary data are available as BioRxiv supplemental files.

bioinformatics↗

bioRxiv2021

Langevin dynamics simulation of protein dynamics in nanopores at microsecond timescales

With rapid advancement in the fields of nanopore analysis of protein, it has become imperative to develop modeling framework for understanding the protein dynamics in nanopores. Such modeling framework should include the effects of electro-osmosis, as it plays significant role during protein translocation in confinement. Currently, the molecular dynamics simulations that include the hydrodynamic effects are limited to a timescale of few 100 ns. These simulations give insight about important events like protein unfolding which occurs in this timescale. But many electrophoresis experiments are limited by a detector resolution of ~ 2.5 s. Analytical theory has been used to interpret protein dynamics at such large timescale. There is a need for molecular modeling of more complex environment and protein shapes which cannot be accounted for by analytical theory. We have developed a framework to study globular protein dynamics in nanopores by using langevin dynamics on a rigid body model of protein and the hydrodynamics is accounted by analytical theory for simple cylindrical nanopore geometry. This framework has been applied to study the dynamics of Ubiquitin translocation in SiNx nanopore by Nir et al26. They have reported 7 times decrease in average dwell time of the protein inside the nanopore in response to a small change in pH from 7.0 to 7.2 and the modification of protein charge was attributed for such drastic change. Closer examination using our simulation revealed that the electro-osmotic effects originating due to very small change in the surface electrostatic potential of the nanopore could lead to such a drastic change in protein dynamics.

biophysics↗