Evidence map›Paper›PMID 36477674›Full record

ArticleNature communications2022

An in silico method to assess antibody fragment polyreactivity.

Edward P Harvey, Jung-Eun Shin, Meredith A Skiba, Genevieve R Nemeth, Joseph D Hurley, Alon Wellner, Ada Y Shaw, Victor G Miranda, Joseph K Min, Chang C Liu and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
–field-weighted citation impact
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

39 citing papers in PubMed.

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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

12 authors.

Edward P Harvey *Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
Jung-Eun Shin *Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Meredith A Skiba *Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
Genevieve R NemethDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
Joseph D HurleyDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.ORCID 0000-0002-3903-318X
Alon WellnerDepartment of Chemistry, University of California, Irvine, CA, 92697, USA.
Ada Y ShawDepartment of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Victor G MirandaDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.ORCID 0000-0001-8631-4622
Joseph K MinDepartment of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Chang C LiuDepartment of Chemistry, University of California, Irvine, CA, 92697, USA.ORCID 0000-0002-3290-2880
Debora S MarksDepartment of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA. Debora_Marks@hms.harvard.edu.ORCID 0000-0001-9388-2281
Andrew C KruseDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA. Andrew_kruse@hms.harvard.edu.ORCID 0000-0002-1467-1222

Funding

Making antibody generation rapid, scalable, and democratic through machine learning and continuous evolutionR01CA260415 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI KRUSE, ANDREW, LIU, CHANG C · 2020 to 2024
$8.4M
Training in Pharmacological SciencesT32GM132089 · NIGMS · HARVARD MEDICAL SCHOOL · PI DAVID E. GOLAN, Timothy J Mitchison · 2019 to 2026
$3.7M
NCI NIH HHS R01 CA260415NIGMS NIH HHS T32 GM132089
6 · The paper itself

Abstract

Antibodies are essential biological research tools and important therapeutic agents, but some exhibit non-specific binding to off-target proteins and other biomolecules. Such polyreactive antibodies compromise screening pipelines, lead to incorrect and irreproducible experimental results, and are generally intractable for clinical development. Here, we design a set of experiments using a diverse naïve synthetic camelid antibody fragment (nanobody) library to enable machine learning models to accurately assess polyreactivity from protein sequence (AUC > 0.8). Moreover, our models provide quantitative scoring metrics that predict the effect of amino acid substitutions on polyreactivity. We experimentally test our models' performance on three independent nanobody scaffolds, where over 90% of predicted substitutions successfully reduced polyreactivity. Importantly, the models allow us to diminish the polyreactivity of an angiotensin II type I receptor antagonist nanobody, without compromising its functional properties. We provide a companion web-server that offers a straightforward means of predicting polyreactivity and polyreactivity-reducing mutations for any given nanobody sequence.

Indexed as

Immunoglobulin FragmentsImmunoglobulin Fragments

Identifiers

PMID36477674
PMCPMC9729196

What OpenQuestion holds

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Registered trials

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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.