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US 12,725,003 B2Granted
Identification of convergent antibody specificity sequence patterns
AssigneeAlloy Therapeutics, Inc.
InventorsSimon Friedensohn, Sai Reddy
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Abstract
The present methods use a variational autoencoder (VAE) and deep generative modelling to learn meaningful representations from the immune repertoires. The system can map input sequences into a lower-dimensional latent space, which reveals a large amount of convergent sequence patterns. The system can identify patterns present in convergent clusters that are highly predictive for antigen exposure and/or antigen specificity. The system can generate, from the latent space, novel functional antibody sequence variants in-silico.
Claims19
A method, comprising:
- providing to a candidate identification system a plurality of input amino acid sequences from a library of immunoglobulin heavy chain variable region (VH) sequences or a library of immunoglobulin light chain variable (VL) region sequences,
- wherein the library comprises an entire immunoglobulin repertoire from animals immunized with an antigen;
- transforming, by an encoder executed by the candidate identification system, the plurality of input amino acid sequences into a latent space,
- wherein the encoder uses a linear classifier, a plurality of rectified linear units, and a variational autoencoder (VAE) to transform the plurality of input amino acid sequences into the latent space, and
- wherein the linear classifier is a linear support vector machine (SVM) classifier of the immunized antigen exposure;
- determining, by a clustering engine executed by the candidate identification system, a plurality of sequence clusters within the latent space;
- identifying, by the clustering engine, a convergent sequence cluster that is predictive for the immunized antigen exposure;
- selecting, by a candidate generation engine executed by the candidate identification system, within the latent space an immunized antigen-associated convergent sequence cluster;
- generating, by the candidate generation engine using a decoder, a candidate amino acid sequence based on the immunized antigen-associated convergent sequence cluster,
- wherein the decoder comprises a plurality of different neural networks comprising a plurality of long short-term recurrent neural networks, and
- wherein generating the candidate amino acid sequence further comprises providing the immunized antigen-associated convergent sequence cluster to each of the plurality of long short-term recurrent neural networks;
- and
- generating a library of hybridoma cell clones expressing antibodies comprising the candidate amino acid sequence.
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