Evidence map›Paper›PMID 35905834›Full record

ArticleGenomics2022

GigaAssay - An adaptable high-throughput saturation mutagenesis assay platform.

Ronald Benjamin, Christopher J Giacoletto, Zachary T FitzHugh, Danielle Eames, Lindsay Buczek, Xiaogang Wu, Jacklyn Newsome, Mira V Han, Tony Pearson, Zhi Wei and 6 more

Open access · goldAbstract read
In one paragraph

Article in Genomics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 13 citations in OpenAlex.

  1. Central Dogma Cycle and Network: A Model for Cell Memory.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  2. Article
  3. Article
  4. New Gain-of-Function Mutations Prioritize Mechanisms of HER2 Activation.medRxiv : the preprint server for health sciences · 2025
    Article
  5. Article
  6. Article
  7. Synonymous Variants of Uncertain Silence.International journal of molecular sciences · 2023
    Article
  8. Article
  9. The history and conceptual framework of assays and screens.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    Article
  10. Article
  11. Article
  12. Article
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 1 country.

Ronald BenjaminNevada Institute of Personalized Medicine, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA.
Christopher J GiacolettoNevada Institute of Personalized Medicine, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA; School of Life Sciences, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA; Heligenics Inc., 833 Las Vegas Blvd. North, Suite B, Las Vegas, NV 89101, USA.
Zachary T FitzHughNevada Institute of Personalized Medicine, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA.
Danielle EamesNevada Institute of Personalized Medicine, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA.
Lindsay BuczekNevada Institute of Personalized Medicine, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA.
Xiaogang WuNevada Institute of Personalized Medicine, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA.
Jacklyn NewsomeNevada Institute of Personalized Medicine, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA.
Mira V HanNevada Institute of Personalized Medicine, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA; School of Life Sciences, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA.
Tony PearsonSchool of Life Sciences, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA; Heligenics Inc., 833 Las Vegas Blvd. North, Suite B, Las Vegas, NV 89101, USA.
Zhi WeiDepartment of Computer Science, New Jersey Institute of Technology, GITC 4214C, University Heights, Newark, NJ 07102, USA.
Atoshi BanerjeeNevada Institute of Personalized Medicine, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA.
Lancer BrownHeligenics Inc., 833 Las Vegas Blvd. North, Suite B, Las Vegas, NV 89101, USA.
Liz J ValenteHeligenics Inc., 833 Las Vegas Blvd. North, Suite B, Las Vegas, NV 89101, USA.
Shirley ShenNevada Institute of Personalized Medicine, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA.
Hong-Wen DengCenter for Biomedical Informatics & Genomics Tulane University, 1440 Canal Street, Suite 1621, New Orleans, LA 70112, USA.
Martin R SchillerNevada Institute of Personalized Medicine, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA; School of Life Sciences, University of Nevada, Las Vegas, 4505 S. Maryland Parkway, Las Vegas, Nevada 89154, USA; Heligenics Inc., 833 Las Vegas Blvd. North, Suite B, Las Vegas, NV 89101, USA. Electronic address: martin.schiller@unlv.edu.
University of Nevada, Las Vegas · USNew Jersey Institute of Technology · USTulane University · US

Funding

The Genome Analysis and Sequencing Pipeline (GASP)P20GM121325 · NIGMS · UNIVERSITY OF NEVADA LAS VEGAS · PI CHEN, JINGCHUN · 2018 to 2022
$11.5M
The C-terminomeR15GM107983 · NIGMS · UNIVERSITY OF NEVADA LAS VEGAS · PI SCHILLER, MARTIN R · 2013 to 2013
$443k
A novel high-throughput functional screen based upon chimeric minimotif decoysR21AI116411 · NIAID · UNIVERSITY OF NEVADA LAS VEGAS · PI SCHILLER, MARTIN R · 2015 to 2016
$407k
High-throughput functional analysis and clinical relevance of all possible variants of a geneR43HG012537 · NHGRI · HELIGENICS INC · PI SCHILLER, MARTIN R. · 2023 to 2023
$399k
Identification of short functional motifs as potential drug targets for HIVR21AI078708 · NIAID · UNIVERSITY OF NEVADA LAS VEGAS · PI SCHILLER, MARTIN R · 2008 to 2009
$368k
HIV Toolbox, an interactive, visual, and customizable HIV Protein OntologyR56AI109156 · NIAID · UNIVERSITY OF NEVADA LAS VEGAS · PI SCHILLER, MARTIN R · 2014 to 2014
$332k
NHGRI NIH HHS R43 HG012537NIAID NIH HHS R21 AI078708NIAID NIH HHS R21 AI116411NIAID NIH HHS R56 AI109156NIGMS NIH HHS P20 GM121325NIGMS NIH HHS R15 GM107983
6 · The paper itself

Abstract

High-throughput assay systems have had a large impact on understanding the mechanisms of basic cell functions. However, high-throughput assays that directly assess molecular functions are limited. Herein, we describe the "GigaAssay", a modular high-throughput one-pot assay system for measuring molecular functions of thousands of genetic variants at once. In this system, each cell was infected with one virus from a library encoding thousands of Tat mutant proteins, with each viral particle encoding a random unique molecular identifier (UMI). We demonstrate proof of concept by measuring transcription of a GFP reporter in an engineered reporter cell line driven by binding of the HIV Tat transcription factor to the HIV long terminal repeat. Infected cells were flow-sorted into 3 bins based on their GFP fluorescence readout. The transcriptional activity of each Tat mutant was calculated from the ratio of signals from each bin. The use of UMIs in the GigaAssay produced a high average accuracy (95%) and positive predictive value (98%) determined by comparison to literature benchmark data, known C-terminal truncations, and blinded independent mutant tests. Including the substitution tolerance with structure/function analysis shows restricted substitution types spatially concentrated in the Cys-rich region. Tat has abundant intragenic epistasis (10%) when single and double mutants are compared.

Indexed as

HIV-1tat Gene Products, Human Immunodeficiency VirusCell LineHIV Long Terminal RepeatMutagenesisTranscriptional Activationtat Gene Products, Human Immunodeficiency VirusHigh-throughput assayIntragenic epistasisProtein structureSaturation mutagenesisTatTranscription

Identifiers

PMID35905834
PMCPMC9420302
OpenAlexW4288045147

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.