Biology subjects

Lossius, A.

Publications and source records attributed to Lossius, A..

3 recordsLinked to original sources

bioRxiv2025

SH2D2A is an indicator of favourable prognosis in bladder cancer and is enriched in Treg cells

Given the expanding availability of RNA-seq and other such high dimensional data it is now possible to consider a complementary approach working in the opposite direction i.e., from transcriptomics up towards protein function. This approach may prove fruitful in producing information on the function of cytosolic-bound proteins such as adapter proteins. To test the validity of this method, we made use of several public datasets to interrogate the cancer-specific role of the adapter protein SH2D2A: a protein enriched in T and NK cells and a known interactor of the kinase LCK, whose function remains uncertain. We found that SH2D2A is a favourable marker for prognosis in urothelial bladder cancer (BLCA). Digging further, we identified a population of SH2D2A+ FOXP3+ IL2RAhi activated Tregs as the main expressors of SH2D2A in BLCA. This suggests that the expression of SH2D2A in these Tregs contributes to a beneficial prognostic effect. Further comprehension of SH2D2As function in these cells holds the potential for advancing treatment in BLCA and diversifying possible targets for immunotherapies.

bioinformatics↗

bioRxiv2024

Ultra-long sequencing for contiguous haplotype resolution of the human immunoglobulin heavy chain locus

Genetic diversity within the human immunoglobulin heavy chain (IGH) locus influences the expressed antibody repertoire and susceptibility to infectious and autoimmune diseases. However, repetitive sequences and complex structural variation pose significant challenges for large-scale characterization. Here, we introduce a method using Oxford Nanopore ultra-long sequencing and adaptive sampling, coupled with a bioinformatic pipeline, to generate haplotype-resolved single-contig IGH assemblies. We compared our method to a well-established IGH characterization framework using Pacific Biosciences HiFi sequencing in four donors and observed almost complete sequence congruence between our haplotype-resolved assemblies and the HiFi reads. Applying our approach to the HG002 reference material revealed no base differences to the Telomere-to-Telomere genome benchmark over the IGH locus. Importantly, among the four donors, our approach uncovered 30 novel alleles and previously uncharacterized large structural variants, including a 120 kb segmental duplication spanning IGHE to IGHA1 and an expanded seven-copy IGHV3-23 gene haplotype.

immunology↗

bioRxiv2021

Stereotyped B-cell responses are linked to IgG constant region polymorphisms in multiple sclerosis

Clonally related B cells infiltrate the brain, meninges and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients, but the mechanisms driving the B-cell response and shaping the immunoglobulin repertoires remain unclear. Here, we used single-cell full-length RNA-seq and B-cell receptor reconstruction to simultaneously assess the phenotypes, isotypes, constant region polymorphisms, and the paired heavy- and light-chain repertoires in intrathecal B-lineage cells. We detected extensive clonal connections between the memory B cell and antibody-secreting cell (ASC) compartments and observed clonally related cells of different isotypes, including IgM/IgG1, IgG1/IgA1, IgG1/IgG2, and IgM/IgA1. There was a strong dominance of the G1m1 allotype constant region polymorphisms in ASCs, but not in memory B cells. Tightly linked to the G1m1 allotype, we found a preferential pairing of the IGHV4 gene family with the {kappa} variable (IGKV)1 gene family. These results link IgG constant region polymorphisms to stereotyped B-cell responses in MS, indicating that the intrathecal B-cell response in these patients could be directed against structurally similar epitopes. The data also suggest that the dominance of the G1m1 allotype in ASCs may occur as a result of biased differentiation of intrathecal memory B cells.

immunology↗