Agnostic detection of genomic alterations by holistic DNA structural interrogation.

There is an established relationship between primary DNA sequence, secondary and tertiary chromatin structure, and transcriptional activity, suggesting that observed differences in one of these properties may reflect changes in the others. Here, we exploit these relationships to show that variations in DNA structure can be used to identify a wide range of genomic alterations in mammalian samples. In this proof-of-concept study we characterized and compared genome-wide histone occupancy by ChIP-Seq, DNA accessibility by ATAC-Seq, and chromosomal conformation by Hi-C for five CRISPR/Cas9-modified mammalian cell lines and their unmodified parent strains, as well as in one modified tissue sample and its parent strain.

Identification of Genomic Alterations Through Multilevel DNA Structural Analysis.

Current methods to identify genomic alterations using whole-genome sequencing (WGS) data are often limited to single nucleotide polymorphisms and insertions and deletions that are less than 10 bp in length. These limitations are largely due to challenges in accurately mapping short sequencing reads that significantly diverge from the reference genome. Newer sequencing-based methods have been developed to define and characterize larger DNA structural elements.

Cell-Free Production of Protein Biologics Within 24 H.

Protein biologics have emerged as a safe and effective group of drug products that can be used in a variety of medical disorders and clinical settings, including treatment of orphan diseases, personalized medicine, and point-of-care applications. However, the full potential of protein biologics for such applications will not be realized until there are methods available for rapid and cost-effective production of small scale products for individual needs. Here, we describe a modular and scalable method for rapid and adaptable production of protein-based medical products at small doses.

Actin exposure upon tissue injury is a targetable wound site-specific protein marker.

Background: Identification of wound-specific markers would represent an important step toward damaged tissue detection and targeted delivery of biologically important materials to injured sites. Such delivery could minimize the amount of therapeutic materials that must be administered and limit potential collateral damage on nearby normal tissues. Yet, biological markers that are specific for injured tissue sites remain elusive.