New paper: light chain sequences derived from RNAseq data
Nau et al. Frontiers in Immunology, 14:1167235 2023
We recently published a manuscript describing a method for identifying antibody light chain variable domain sequences from untargeted RNAseq data, which is available from the open-access journal Frontiers in Immunology. This is the result of work by Allison Nau, who started in the lab as a student on the BU MS in Bioinformatics program and continued to work on the project after graduation.
Each patient with AL amyloidosis has a unique involved antibody light chain protein that aggregates to form amyloid fibrils, and a major challenge is to work out why these light chains aggregate but most others do not. One way to do this is to study light chains that do not aggregate despite circulating at high levels, such as those found in multiple myeloma. However, determining light chain sequences is slow and costly. To get around this problem, we asked whether we could extract light chain sequences from existing RNAseq datasets using the program MiXCR.
Our approach worked well enough to apply it to a large set of sequence data from a study by the Multiple Myeloma Research Foundation (MMRF), where hundreds of myeloma patients had their cancer cells sequenced in order to look for factors that influence disease progression and responses to therapy. We were able to identify over 700 light chain sequences from the MMRF data, which is more than twice the number of sequences that we had previously known.
All of these sequences are now deposited in AL-Base, our website that brings together light chain sequences for further study. We are currently in the process of updating AL-Base and analyzing the new data to ask what these new sequences reveal about the factors that lead to amyloidosis.
The work described in this paper was supported by the Karin Grunebaum Cancer Research Foundation and by pilot funding from BU, including an American Cancer Society Institutional Research Grant and the Clinical and Translational Sciences Institute. Allison was also supported by the BU Bioinformatics Program and the BU Genome Science Institute via the Bioinformatics Masters Summer Internship Program.