# Validated Negative Regions (VNRs) in the VISTA Database might be Truncated Forms of Bona Fide Enhancers

## TL;DR

This paper suggests that validated negative regions in the VISTA database might be shortened versions of real enhancers, similar to validated positive regions.

## Contribution

The study proposes that VNRs, like VPRs, could be truncated forms of long enhancers based on shared evolutionary and epigenetic features.

## Key findings

- VNRs show similar evolutionary constraints and chromatin modification patterns to VPRs.
- VNRs are on average half as long as predicted enhancers and overlap with conserved enhancer regions.
- VNRs and VPRs have similar in silico mutagenesis impact score spectra.

## Abstract

The VISTA enhancer database is a valuable resource for evaluating predicted enhancers in humans and mice. In addition to thousands of validated positive regions (VPRs) in the human and mouse genomes, the database also contains similar numbers of validated negative regions (VNRs). It is previously shown that the VPRs are on average half as long as predicted overlapping enhancers that are highly conserved and hypothesize that the VPRs may be truncated forms of long bona fide enhancers. Here, it is shown that like the VPRs, the VNRs also are under strong evolutionary constraints and overlap predicted enhancers in the genomes. The VNRs are also on average half as long as predicted overlapping enhancers that are highly conserved. Moreover, the VNRs and the VPRs display similar cell/tissue‐specific modification patterns of key epigenetic marks of active enhancers. Furthermore, the VNRs and the VPRs show similar impact score spectra of in silico mutagenesis. These highly similar properties between the VPRs and the VNRs suggest that like the VPRs, the VNRs may also be truncated forms of long bona fide enhancers.

The VISTA enhancer database contains thousands of validated positive regions (VPRs) and validated negative regions (VNRs). It is suggested that VPRs may be truncated forms of long bona fide enhancers. As VNRs exhibit similar evolutionary constraints and chromatin modification patterns to VPRs, like VPRs, VNRs may be also truncated forms of long bona fide enhancers.