{"id":1450,"date":"2026-03-06T09:37:56","date_gmt":"2026-03-06T08:37:56","guid":{"rendered":"https:\/\/bdagroup.nl\/?post_type=internship&#038;p=1450"},"modified":"2026-05-18T16:14:10","modified_gmt":"2026-05-18T14:14:10","slug":"dissecting-b-cell-differentation-with-multi-omics-single-cell-analysis","status":"publish","type":"internship","link":"https:\/\/bdagroup.nl\/?internship=dissecting-b-cell-differentation-with-multi-omics-single-cell-analysis","title":{"rendered":"DISSECTING B CELL DIFFERENTATION WITH MULTI-OMICS SINGLE-CELL ANALYSIS"},"content":{"rendered":"\n<p>The generation of long-lasting high affinity antibodies is one of the core pillars of our immune system ensuring life-long protection against infection. Dysregulation of this process can cause severe pathological conditions, such as alloimmunization during blood transfusions or self-reactivity in auto-immune disease. &nbsp;High affinity antibodies are formed as product of a <em>germinal center<\/em> (GC) reaction, in which activated B cells proliferate and differentiated into antibodies-secreting cells (ASC). Understanding the exact mechanisms controlling this process within the GC is fundamental to devise strategies to modulate antibodies formation in both health and disease<\/p>\n\n\n\n<p>During the past Sars-CoV2 pandemic we had the unique opportunity to investigate B cell differentiation dynamics in human settings by specifically analyzing Sars-CoV2 spike-specific B cells isolated from infected individuals or individuals undergoing mRNA vaccination. In particular, we generated a multi-omics single-cell dataset containing more than 40\u2019000 spike-specific B cells from 24 individuals at three timepoints after vaccination of which we analyzed transcriptome, surface protein expression and B-cell receptor (BCR) sequence.<\/p>\n\n\n\n<p>The aim of this project is to use this multi-omics single cell dataset to delineate B cell differentiation pathways by coupling transcriptome-based trajectory inference (also-called <em>pseudotime<\/em>) with BCR-based clonal lineages. The first, which is a general single-cell analysis approach, tries order cells along a continuous progression path leveraging on minor transcriptomic differences among cells. The latter, which is applicable only to B cells, leverages the sequence of the B cell receptor (BCR), which is unique to each B cell and inherited by its progeny, to reconstruct lineage trees of single B cell responses. These trees are inferred from the accumulation of mutations in the BCR sequence (somatic hypermutations, SHM) that arise during the germinal center reaction, where B cells iteratively mutate and are selected for improved antigen binding.<\/p>\n\n\n\n<p>Your task within this project will be to evaluate which is the best computational approach to reconstruct BCR-based clonal lineages starting from single-cell data. You will be testing selected recently published methodologies on our spike-specific B cells datasets and perform comparative analysis on the obtained reconstructed lineages. Knowledge of R\/Phyton is required. &nbsp;<\/p>\n","protected":false},"template":"","categories":[],"tags":[],"class_list":["post-1450","internship","type-internship","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/bdagroup.nl\/index.php?rest_route=\/wp\/v2\/internship\/1450","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/bdagroup.nl\/index.php?rest_route=\/wp\/v2\/internship"}],"about":[{"href":"https:\/\/bdagroup.nl\/index.php?rest_route=\/wp\/v2\/types\/internship"}],"wp:attachment":[{"href":"https:\/\/bdagroup.nl\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1450"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bdagroup.nl\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1450"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bdagroup.nl\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1450"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}