The Stanford University HIV Drug Resistance Database is a curated public database designed to represent, store, and analyze the different forms of data underlying HIVs drug resistance. HIVDB has three main types of content: (1) Database queries and references, (2) Interactive programs, and (3) Educational resources. Database queries are designed primarily for researchers studying HIV drug resistance. The interactive programs and educational resources are designed for both researchers and those wishing to learn more about HIV drug resistance. 1.DATABASE QUERY AND REFERENCE PAGES Genotype-Treatment Correlations This Genotype-Treatment section of the database links to 15 interactive query pages that explore the relationship between treatment with HIV-1 antiretroviral drugs (ARVs) and mutations in HIV reverse transcriptase (RT), protease, and integrase. There are five types of interactive query pages: Treatment Profiles (Protease and RT inhibitors) Mutation Profiles (Protease and RT mutations) Detailed Treatment Queries (Protease, RT, and integrase inhibitors) Detailed Mutation Queries (Protease, RT, and integrase mutations) Mutation Prevalence According to Subtype and Treatment Genotype-Phenotype Correlations The main page of the Genotype-Phenotype Correlations section links to four interactive query pages: three dynamically updated data summaries and one regularly updated downloadable dataset. Drug Resistance Positions Query for levels of resistance associated with known drug resistance mutations Detailed Phenotype Queries Queries for levels of resistance associated with individual mutations or mutation combinations at all positions of protease, RT, and integrase Patterns of Drug Resistance Mutations Downloadable Reference Dataset Genotype-Clinical Correlations This part of the database has two main sections: Clinical Trials Datasets Summaries of Clinical Studies References This part of the database has two main sections: one with summaries of the data from each of the references in HIVDB and one in which every primate immunodeficiency virus sequence in GenBank is annotated according to its presence or absence in HIVDB. Studies in HIVDB GenBank HIVDB New Submissions Approximately every three months, the New Submissions section lists the studies that have been entered into HIVDB. The study title links to the introductory page of the study in the References section. Database Statistics (http://hivdb.stanford.edu/pages/HIVdbStatistics.html) 2. INTERACTIVE PROGRAMS HIVDB has seven main interactive programs. 1. HIVdb Program Mutation List Analysis Sequence Analysis HIVdb Output Sierra Web Service Release Notes Algorithm Specification Interface (ASI) 2. HIValg Program 3. HIVseq Program 4. Calibrated Population Resistance (CPR) tool 5. Mutation ARV Evidence Listing (MARVEL) 6. ART-AiDE 7. Rega HIV-1 Subtyping tool Three programs in the HIV Drug Resistance Database share a common code base: HIVseq, HIVdb, and HIValg. HIVseq accepts user-submitted protease, RT, and integrase sequences, compares them to the consensus subtype B reference sequence, and uses the differences as query parameters for interrogating the HIV Drug Resistance database (Shafer, D Jung, & B Betts, Nat Med 2000; Rhee SY et al. AIDS 2006). The query result provides users with the prevalence of protease, RT and integrase mutations according to subtype and PI, nucleoside RT inhibitor (NRTI), non-nucleoside RT inhibitor (NNRTI), and integrase inhibitor (INI) exposure. This allows users to detect unusual sequence results immediately so that the person doing the sequencing can check the primary sequence output while it is still on the desktop. In addition, unexpected associations between sequences or isolates can be discovered by immediately retrieving data on isolates sharing one or more mutations with the sequence. There are three ways in which the HIVdb program can be used: (i) entering a list of protease and RT mutations, (ii) entering a complete sequence containing protease, RT, and/or integrase, and (iii) using a Web Service. HIVdb is an expert system that accepts user-submitted HIV-1 pol sequences and returns inferred levels of resistance to 20 FDA-approved ARV drugs including 8 PIs, 7 NRTIs, 4 NNRTIs, and - with this update - one INI. In the HIVdb system, each HIV-1 drug resistance mutation is assigned a drug penalty score and a comment; the total score for a drug is derived by adding the scores of each mutation associated with resistance to that drug. Using the total drug score, the program reports one of the following levels of inferred drug resistance: susceptible, potential low-level resistance, low-level resistance, intermediate resistance, and high-level resistance. HIValg is designed for users interested in comparing the results of different algorithms or who are interested in comparing and evaluating existing and newly developed algorithms. The ability to develop new algorithms that can be run on the HIV Drug Resistance Database depends on the Algorithm Specific Interface (ASI) compiler (Shafer & Betts JCM 2003). Submission of Sequences and Mutations For each of the three programs, sequences can be entered using either the Sequence Analysis Form or the Mutation List form. 3. EDUCATIONAL RESOURCES HIVDB contains several regularly updated sections summarizing data linking RT, protease, and integrase mutations and antiretroviral drugs (ARVs). These sections include (i) tabular summaries of the major mutations associated with each ARV class, (ii) detailed summaries of the major, minor, and accessory mutations associated with each ARV, (iii) the comments used by the HIVdb program, (iv) the scores used by the HIVdb program, (v) clinical studies in which baseline drug resistance mutations have been correlated with the virological response (clinical outcome) to a specific ARV, (vi) mutations that can be used for drug resistance surveillance, and (vii) a two-page PDF handout. 1. Drug Resistance Summaries Tabular Drug Resistance Summaries by ARV Class Detailed Drug Resistance Summaries by ARV Drug Resistance Mutation Comments Used by the HIVdb Program Drug Resistance Mutation Scores Used by the HIVdb Program Genotype-Clinical Outcome Correlation Studies 2. Surveillance Drug-Resistance Mutation List Section 3. PDF Handout Grant Support 1. National Institute for Allergy and Infectious Diseases (NIAID, NIH): Online HIV Drug Resistance Database (PI: Robert W. Shafer, MD, 1R01AI68581-01A1), 04/01/06 - 3/31/11 2. National Institute for Allergy and Infectious Diseases (NIAID, NIH) supplement to the grant Identification of Multidrug-Resistant HIV-1 Isolates (PI: Robert W. Shafer, MD, AI46148-01): Supplement provided 1999-2005. 3. NIH/NIGMS Program Project on AIDS Structural Biology Program Project: Targeting Ensembles of Drug Resistant Protease Variants (PI: Celia Schiffer, PhD, University of Massachusetts): 2002-2007 4. University-wide AIDS Research Program (CR03-ST-524). Community collaborative award: Optimizing Clinical HIV Genotypic Resistance Interpretation: Principal Investigators: Robert W. Shafer, MD and W. Jeffrey Fessel MD (Kaiser Permanente Medical Care Program): 2004-2005 5. Stanford University Bio-X Interdisciplinary Initiative: HIV Gene Sequence Analysis for Drug Resistance Studies: A Pharmacogenetic Challenge Principal Investigators: Robert W. Shafer, MD and Daphne Koller, Ph.D. (Computer Science): 2000-2002

This dataset was used by the NCI's Quantitative Imaging Network (QIN) PET-CT Subgroup for their project titled: Multi-center Comparison of Radiomic Features from Different Software Packages on Digital Reference Objects and Patient Datasets. The purpose of this project was to assess the agreement among radiomic features when computed by several groups by using different software packages under very tightly controlled conditions, which included common image data sets and standardized feature definitions. The image datasets (and Volumes of Interest – VOIs) provided here are the same ones used in that project and reported in the publication listed below (ISSN 2379-1381 https://doi.org/10.18383/j.tom.2019.00031). In addition, we have provided detailed information about the software packages used (Table 1 in that publication) as well as the individual feature value results for each image dataset and each software package that was used to create the summary tables (Tables 2, 3 and 4) in that publication. For that project, nine common quantitative imaging features were selected for comparison including features that describe morphology, intensity, shape, and texture and that are described in detail in the International Biomarker Standardisation Initiative (IBSI, https://arxiv.org/abs/1612.07003 and publication (Zwanenburg A. Vallières M, et al, The Image Biomarker Standardization Initiative: Standardized Quantitative Radiomics for High-Throughput Image-based Phenotyping. Radiology. 2020 May;295(2):328-338. doi: https://doi.org/10.1148/radiol.2020191145). There are three datasets provided – two image datasets and one dataset consisting of four excel spreadsheets containing feature values.

1. The first image dataset is a set of three Digital Reference Objects (DROs) used in the project, which are: (a) a sphere with uniform intensity, (b) a sphere with intensity variation (c) a nonspherical (but mathematically defined) object with uniform intensity. These DROs were created by the team at Stanford University and are described in (Jaggi A, Mattonen SA, McNitt-Gray M, Napel S. Stanford DRO Toolkit: digital reference objects for standardization of radiomic features. Tomography. 2019;6:–.) and are a subset of the DROs described in DRO Toolkit. Each DRO is represented in both DICOM and NIfTI format and the VOI was provided in each format as well (DICOM Segmentation Object (DSO) as well as NIfTI segmentation boundary).
2. The second image dataset is the set of 10 patient CT scans, originating from the LIDC-IDRI dataset, that were used in the QIN multi-site collection of Lung CT data with Nodule Segmentations project ( https://doi.org/10.7937/K9/TCIA.2015.1BUVFJR7 ). In that QIN study, a single lesion from each case was identified for analysis and then nine VOIs were generated using three repeat runs of three segmentation algorithms (one from each of three academic institutions) on each lesion. To eliminate one source of variability in our project, only one of the VOIs previously created for each lesion was identified and all sites used that same VOI definition. The specific VOI chosen for each lesion was the first run of the first algorithm (algorithm 1, run 1). DICOM images were provided for each dataset and the VOI was provided in both DICOM Segmentation Object (DSO) and NIfTI segmentation formats.
3. The third dataset is a collection of four excel spreadsheets, each of which contains detailed information corresponding to each of the four tables in the publication. For example, the raw feature values and the summary tables for Tables 2,3 and 4 reported in the publication cited (https://doi.org/10.18383/j.tom.2019.00031). These tables are:

Software Package details : This table contains detailed information about the software packages used in the study (and listed in Table 1 in the publication) including version number and any parameters specified in the calculation of the features reported. DRO results : This contains the original feature values obtained for each software package for each DRO as well as the table summarizing results across software packages (Table 2 in the publication) . Patient Dataset results: This contains the original feature values for each software package for each patient dataset (1 lesion per case) as well as the table summarizing results across software packages and patient datasets (Table 3 in the publication). Harmonized GLCM Entropy Results : This contains the values for the “Harmonized” GLCM Entropy feature for each patient dataset and each software package as well as the summary across software packages (Table 4 in the publication).