Mutation and Site-specific Selection Driving B Cell Affinity Maturation is Consistent Across...
summary
Deep Illumina sequencing of the CDR3 region (5 million reads per person, 130 nt) is used to fit separate nucleotide substitution matrices for V, D and J segments and to compare branch-length multipliers (D ≈ 3–4× V, J ≈ 0.6× V), consistent across three healthy individuals. Unproductive out-of-frame sequences as neutral baseline calibrate context-dependent mutation rates, and sitewise selection maps come from renaissance counting with empirical Bayes regularization (sampling mutation histories; analyses take days on EC2/Spark). Results show pervasive purifying selection with focal diversifying sites and a conserved aromatic residue near the cysteine.
AI-written summary · about
chapters (15)
- 0:00Introduction
- 2:05Vaccine Development Without Disease Exposure
- 2:31Biological Background
- 6:04Goals
- 13:06Different Models
- 16:37Branch Length
- 21:20Subpopulations
- 22:57Principal Components
- 24:24Gene Subgroups
- 26:48Mutational Process
- 28:31Renaissance Accounting
- 29:46Smoking Survey
- 30:27Model
- 37:15Funding
- 37:51Classification
related talks
30mProfiling of Antibody Repertoires and Immunoglobulin Loci Enables Large-Scale Analysis of...
48mVariation in Regulatory Information Within and Between Species
43mAlgorithms for Inferring Phenotypes from Ancient DNA
01h 03mIntroduction to Cancer Bioinformatics II: Tumor Phylogeny
42mPython’s role in accelerating biomedical science
27mPredicting the Deleteriousness of Genomic Variants – Big and Small
57mBig Data and New Models Needed to Study DNA Variation in Evolution and Cancer
32mMachine Learning-Based Design Of Proteins