HIResist is a database that has been developed to facilitate a better understanding of the interactions between the HIV-1 envelope protein (ENV) and broadly neutralizing antibodies (bnAbs). The database has been created by the Herschhorn Lab at the University of Minnesota and provides a user-friendly platform to both bioinformaticians and experimentalists to access public databases, as well as computational tools for the analysis of HIV-1 resistance to bnAbs and the pathways of interaction.

All data are currently sourced from publicly available databases, such as GenBank and the HIV CATNAP and HIV Antibody Feature databases at the Los Alamos National Laboratory.

The "Search Database" menu item in the "Data" menu allows users to retrieve virus- and antibody-specific information from the locally stored HIV CATNAP database. In addition, users can also search for the CATNAP assay data by providing the virus and the antibody name.

The sequences of a strain of interest can be retrieved by using the "Search Database" feature under the "Data" menu. After typing/selecting the strain of interest from the drop-down list, click the "Submit" button. This will display a page that shows pairwise CATNAP alignment with the HXBc2 reference sequence. Upon scrolling down this page also contains nucleotide and amino acid sequence information for the strain, which can be copied on to the clipboard by clicking on the icon at the top right hand corner.

The bnAb Reactivity tool is designed to facilitate the comparison of the resistance of various HIV-1 strains against different bnAbs. Users can select an antibody from a dropdown menu and choose an ENV feature to include in the result, along with the type of assay (IC₅₀ or IC₈₀) and the desired threshold geometric mean (gMean) value. Strains with gMeans greater than or equal to the selected threshold are considered resistant and those with gMeans below the threshold are considered sensitive. The envelope features are indicated by a black circle (*) above the HXBc2 reference sequence. Clicking on each strain opens a new tab with strain-specific information.

The Strain Sensitivity tool provides users with the option to search for the desired strain using a dropdown menu and select the assay of interest (either IC₅₀ or IC₈₀). While the default threshold concentration is 10 µg/mL, users may select a different value either on the slider or in the text box. Antibodies with gMeans greater than or equal to the selected threshold are considered resistance antibodies while those with gMeans below the threshold are considered sensitivity antibodies.

The "Assays" column refers to the number of experimental references used in calculating the geometric mean (gMean) of IC₅₀ and IC₈₀ values. This statistical approach aids in obtaining a representative estimation of the compound's potency, reflecting the consensus of multiple independent experimental results.

The Cross-Sensitivity tool allows users to compare the neutralization values of two antibodies against a number of strains. The user-selected threshold concentration will separate the plot to show strains that are resistant and sensitive to both antibodies, as well as those that are resistant to one and sensitive to the other. The log scale can be toggled on or off for different visual perspectives.

The interactive plots on these pages allow users to easily view corresponding information by hovering over the data points. Additional tools that are available by hovering over the plots appear on the top right-hand corner of the screen. These tools include:

The "Env Domain" panel displays specific regions within the envelope glycoprotein (consisting of gp120 and gp41) of HIV-1 strains. The definition of these regions is based on the HXBc2 reference sequence and is displayed on the alignments obtained with the bnAb Reactivity tool under the "Tools" tab, as well as in pairwise alignments in the Search Database tool under the "Data" tab. In HIResist, the signal peptide, the variable loops of gp120, and gp41 regions are labeled using different shades of blue, while the constant regions are highlighted in red. The Env Domain starting and ending positions were obtained from the HXB2 Feature Database.

The HXBc2 based starting and ending positions for the Env domains are as follows: