ArticleScience advances2016
Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting.
Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 116 citations in OpenAlex.
- T Cell Thoughts.Immunological reviews · 2026Review
- Article
- RNA-Based High-Throughput Sequencing of the Human Immunoglobulin Repertoire.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Article
- Benchmarking and integrating human B-cell receptor genomic and antibody proteomic profiling.NPJ systems biology and applications · 2024Article
- Inference of annealed protein fitness landscapes with AnnealDCA.PLoS computational biology · 2024Article
- The multilevel extensive diversity across the cynomolgus macaque captured by ultra-deep adaptive immune receptor repertoire sequencing.Science advances · 2024Article
- Article
- Current advancements in B-cell receptor sequencing fast-track the development of synthetic antibodies.Molecular biology reports · 2024Review
- The inhibitory receptor Siglec-G controls the severity of chronic lymphocytic leukemia.EMBO reports · 2023Article
- Dietary restriction mitigates the age-associated decline in mouse B cell receptor repertoire diversity.Cell reports · 2023Article
- Applications of High-Throughput DNA Sequencing to Single-Domain Antibody Discovery and Engineering.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Determining immunoglobulin-specific B cell receptor repertoire of murine splenocytes by next-generation sequencing.STAR protocols · 2022Article
- Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals.Nature communications · 2022Review
- TCRpower: quantifying the detection power of T-cell receptor sequencing with a novel computational pipeline calibrated by spike-in sequences.Briefings in bioinformatics · 2022Article
- Article
- Adaptive Immune Receptor Repertoire (AIRR) Community Guide to TR and IG Gene Annotation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Individualized VDJ recombination predisposes the available Ig sequence space.Genome research · 2021Article
- Targeting B cells in the pre-phase of systemic autoimmunity globally interferes with autoimmune pathology.iScience · 2021Article
- A Bayesian model based computational analysis of the relationship between bisulfite accessible single-stranded DNA in chromatin and somatic hypermutation of immunoglobulin genes.PLoS computational biology · 2021Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-throughput antibody repertoire sequencing (Ig-seq) provides quantitative molecular information on humoral immunity. However, Ig-seq is compromised by biases and errors introduced during library preparation and sequencing. By using synthetic antibody spike-in genes, we determined that primer bias from multiplex polymerase chain reaction (PCR) library preparation resulted in antibody frequencies with only 42 to 62% accuracy. Additionally, Ig-seq errors resulted in antibody diversity measurements being overestimated by up to 5000-fold. To rectify this, we developed molecular amplification fingerprinting (MAF), which uses unique molecular identifier (UID) tagging before and during multiplex PCR amplification, which enabled tagging of transcripts while accounting for PCR efficiency. Combined with a bioinformatic pipeline, MAF bias correction led to measurements of antibody frequencies with up to 99% accuracy. We also used MAF to correct PCR and sequencing errors, resulting in enhanced accuracy of full-length antibody diversity measurements, achieving 98 to 100% error correction. Using murine MAF-corrected data, we established a quantitative metric of recent clonal expansion-the intraclonal diversity index-which measures the number of unique transcripts associated with an antibody clone. We used this intraclonal diversity index along with antibody frequencies and somatic hypermutation to build a logistic regression model for prediction of the immunological status of clones. The model was able to predict clonal status with high confidence but only when using MAF error and bias corrected Ig-seq data. Improved accuracy by MAF provides the potential to greatly advance Ig-seq and its utility in immunology and biotechnology.
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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.