Multi-omics integration to understand the immune system

To establish a better understanding of how inter-individual variability relates to the susceptibility to immune-mediated diseases, and thereby gain a better prioritization of new therapeutic targets, there is an urgent need to characterize the inter-individual variation of immune responses in the human population and to identify the impact of genetic and non-genetic factors on immune variation. To this end, this thesis is divided into two major sections with different focus. The first section investigates genetic, environmental, and metabolic determinants of immune function in both healthy and disease cohorts. In this section, we investigated immune dominators in health and diseases. We applied researches with the Human Functional Genomics Project (HFGP), which aims to systematically and comprehensively study inter-individual variation of human immune parameters and function by combining multi-omics data with deep immune phenotyping in health and diseases.The second section studies the transcriptional responses in immune-mediated diseases. In this section, we presents researches on transcriptome level in infectious disease and autoimmune diseases context. By performing transcriptional studies at both “bulk” and single-cell level, we improved our understanding of the genes and pathways altered in the infectious and autoimmune disease context

q-Analogues of π\pi-Series by Applying Carlitz Inversions to q-Pfaff-Saalschutz Theorem

By applying multiplicate forms of the Carlitz inverse series relations to the $q$-Pfaff-Saalschtz summation theorem, we establish twenty five nonterminating $q$-series identities with several of them serving as $q$-analogues of infinite series expressions for $\pi$ and $1/\pi$, including some typical ones discovered by Ramanujan (1914) and Guillera

Moments on Catalan numbers

AbstractBy combining inverse series relations with binomial convolutions and telescoping method, moments of Catalan numbers are evaluated, which resolves a problem recently proposed by Gutiérrez et al. [J.M. Gutiérrez, M.A. Hernández, P.J. Miana, N. Romero, New identities in the Catalan triangle, J. Math. Anal. Appl. 341 (1) (2008) 52–61]

Multi-Omics Approaches in Immunological Research

The immune system plays a vital role in health and disease, and is regulated through a complex interactive network of many different immune cells and mediators. To understand the complexity of the immune system, we propose to apply a multi-omics approach in immunological research. This review provides a complete overview of available methodological approaches for the different omics data layers relevant for immunological research, including genetics, epigenetics, transcriptomics, proteomics, metabolomics, and cellomics. Thereafter, we describe the various methods for data analysis as well as how to integrate different layers of omics data. Finally, we discuss the possible applications of multi-omics studies and opportunities they provide for understanding the complex regulatory networks as well as immune variation in various immune-related diseases

Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells From Pediatric Coeliac Disease Patients Suggests Potential Pre-Seroconversion Markers

Celiac Disease (CeD) is a complex immune disorder involving villous atrophy in the small intestine that is triggered by gluten intake. Current CeD diagnosis is based on late-stage pathophysiological parameters such as detection of specific antibodies in blood and histochemical detection of villus atrophy and lymphocyte infiltration in intestinal biopsies. To date, no early onset biomarkers are available that would help prevent widespread villous atrophy and severe symptoms and co-morbidities. To search for novel CeD biomarkers, we used single-cell RNA sequencing (scRNAseq) to investigate PBMC samples from 11 children before and after seroconversion for CeD and 10 control individuals matched for age, sex and HLA-genotype. We generated scRNAseq profiles of 9559 cells and identified the expected major cellular lineages. Cell proportions remained stable across the different timepoints and health conditions, but we observed differences in gene expression profiles in specific cell types when comparing patient samples before and after disease development and comparing patients with controls. Based on the time when transcripts were differentially expressed, we could classify the deregulated genes as biomarkers for active CeD or as potential pre-diagnostic markers. Pathway analysis showed that active CeD biomarkers display a transcriptional profile associated with antigen activation in CD4+ T cells, whereas NK cells express a subset of biomarker genes even before CeD diagnosis. Intersection of biomarker genes with CeD-associated genetic risk loci pinpointed genetic factors that might play a role in CeD onset. Investigation of potential cellular interaction pathways of PBMC cell subpopulations highlighted the importance of TNF pathways in CeD. Altogether, our results pinpoint genes and pathways that are altered prior to and during CeD onset, thereby identifying novel potential biomarkers for CeD diagnosis in blood

Revealing missing human protein isoforms based on Ab initio prediction, RNA-seq and proteomics

Biological and biomedical research relies on comprehensive understanding of protein-coding transcripts. However, the total number of human proteins is still unknown due to the prevalence of alternative splicing. In this paper, we detected 31,566 novel transcripts with coding potential by filtering our ab initio predictions with 50 RNA-seq datasets from diverse tissues/cell lines. PCR followed by MiSeq sequencing showed that at least 84.1% of these predicted novel splice sites could be validated. In contrast to known transcripts, the expression of these novel transcripts were highly tissue-specific. Based on these novel transcripts, at least 36 novel proteins were detected from shotgun proteomics data of 41 breast samples. We also showed L1 retrotransposons have a more significant impact on the origin of new transcripts/genes than previously thought. Furthermore, we found that alternative splicing is extraordinarily widespread for genes involved in specific biological functions like protein binding, nucleoside binding, neuron projection, membrane organization and cell adhesion. In the end, the total number of human transcripts with protein-coding potential was estimated to be at least 204,950.publishedVersio