Enhancing sequence alignment of adaptive immune receptors through multi-task deep learning

Thomas Konstantinovsky1,2, Ayelet Peres1,2,3, Ran Eisenberg4

  • 1Department of Bioengineering, Faculty of Engineering, Bar Ilan University, 5290002 Ramat Gan, Israel.

PubMed

Sequence alignment of immunoglobulin (Ig) sequences is central to the computational analysis of adaptive immune receptor repertoire sequencing (AIRR-seq) data, impacting adaptive immunity research and antibody engineering. Traditional Ig sequence aligners often struggle to handle the complexities of V(D)J recombination and somatic hypermutation (SHM), resulting in suboptimal allele assignment accuracy and sequence segmentation. We introduce AlignAIR, a novel deep learning-based aligner that leverages advanced simulation approaches and a multi-task learning framework. AlignAIR sets new state-of-the-art results in allele assignment accuracy, productivity assessments, sequence segmentation, and speed. The model's latent space captures SHM characteristics, offering more profound insights into sequence variability. AlignAIR is designed for seamless integration with existing AIRR-seq pipelines and includes a user-friendly web interface and a container image for efficient local processing of millions of sequences. AlignAIR represents a significant advancement in immunogenetics research and antibody engineering, providing a critical resource for analyzing adaptive immune receptor repertoires.

Related Concept Videos

Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
808
Improving Translational Accuracy02:07

Improving Translational Accuracy

Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
11.9K
Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
4.4K