A Machine Learning Approach for High-Dimensional Time-to-Event Prediction With Application to Immunogenicity of Biotherapies in the ABIRISK Cohort

Predicting immunogenicity for biotherapies using patient and drug-related factors represents nowadays a challenging issue. With the growing ability to collect massive amount of data, machine learning algorithms can provide efficient predictive tools. From the bio-clinical data collected in the multi-cohort of autoimmune diseases treated with biotherapies from the ABIRISK consortium, we evaluated the predictive power of a custom-built random survival forest for predicting the occurrence of anti-drug antibodies. This procedure takes into account the existence of a population composed of immune-reactive and immune-tolerant subjects as well as the existence of a tiny expected proportion of relevant predictive variables. The practical application to the ABIRISK cohort shows that this approach provides a good predictive accuracy that outperforms the classical survival random forest procedure. Moreover, the individual predicted probabilities allow to separate high and low risk group of patients. To our best knowledge, this is the first study to evaluate the use of machine learning procedures to predict biotherapy immunogenicity based on bioclinical information. It seems that such approach may have potential to provide useful information for the clinical practice of stratifying patients before receiving a biotherapy.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

Related Links:

Authors: Luo Y, Xiao R Abstract Scleroderma (systemic sclerosis; SSc) is a complex and highly heterogeneous multisystem rheumatic disease characterized by vascular abnormality, immunologic derangement, and excessive deposition of extracellular matrix (ECM) proteins. To date, the etiology of this life-threatening disorder remains not fully clear. More and more studies show epigenetic modifications play a vital role. The aberrant epigenetic status of certain molecules such as Fli-1, BMPRII, NRP1, CD70, CD40L, CD11A, FOXP3, KLF5, DKK1, SFRP1, and so on contributes to the pathogenesis of progressive vasculopathy, autoi...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Authors: Chan VS Abstract Multiple sclerosis (MS) is an aggravating autoimmune disease that cripples young patients slowly with physical, sensory and cognitive deficits. The break of self-tolerance to neuronal antigens is the key to the pathogenesis of MS, with autoreactive T cells causing demyelination that subsequently leads to inflammation-mediated neurodegenerative events in the central nervous system. The exact etiology of MS remains elusive; however, the interplay of genetic and environmental factors contributes to disease development and progression. Given that genetic variation only accounts for a fraction ...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Epigenetics in Primary Sjögren's Syndrome. Adv Exp Med Biol. 2020;1253:285-308 Authors: Bordron A, Devauchelle-Pensec V, Le Dantec C, Capdeville A, Brooks WH, Renaudineau Y Abstract Primary Sjögren's syndrome (SjS) is a chronic and systemic autoimmune epithelitis with predominant female incidence, which is characterized by exocrine gland dysfunction. Incompletely understood, the etiology of SjS is multi-factorial and evidence is growing to consider that epigenetic factors are playing a crucial role in its development. Independent from DNA sequence mutations, epigenetics is described as inheri...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Authors: Xie Z, Chang C, Huang G, Zhou Z Abstract Type 1 diabetes (T1D) is an autoimmune disease caused by the interaction between genetic alterations and environmental factors. More than 60 susceptible genes or loci of T1D have been identified. Among them, HLA regions are reported to contribute about 50% of genetic susceptibility in Caucasians. There are many environmental factors involved in the pathogenesis of T1D. Environmental factors may change the expression of genes through epigenetic mechanisms, thus inducing individuals with susceptible genes to develop T1D; however, the underlying mechanisms remain ...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Authors: Shao S, Gudjonsson JE Abstract Psoriasis is a chronic and recurrent inflammatory skin disease, involving the rapid proliferation and abnormal differentiation of keratinocytes and activation of T cells. It is generally accepted that the central pathogenesis of psoriasis is a T cell-dominant immune disorder affected by multiple factors including genetic susceptibility, environmental factors, innate and adaptive immune responses, etc. However, the exact etiology is largely unknown. In recent years, epigenetic involvements, such as the DNA methylation, chromatin modifications, and noncoding RNA regulation are ...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Authors: Wu H, Chang C, Lu Q Abstract Systemic lupus erythematosus (SLE) is a life-threatening autoimmune disease that is characterized by dysregulated dendritic cells, T and B cells, and abundant autoantibodies. The pathogenesis of lupus remains unclear. However, increasing evidence has shown that environment factors, genetic susceptibilities, and epigenetic regulation contribute to abnormalities in the immune system. In the past decades, several risk gene loci have been identified, such as MHC and C1q. However, genetics cannot explain the high discordance of lupus incidence in homozygous twins. Environmental fact...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Authors: Chang C, Wu H, Lu Q Abstract Food allergy is a global health problem, particularly in developed countries. It is mainly mediated by Th2 cell and IgE produced by B cells. While the pathogenesis of IgE-mediated food allergy is quite straightforward, the factors that lead to the development of food allergies at any age in children and adults are unclear. Recent studies have revealed that genetics, epigenetics, and environmental exposures contribute to the development of atopy. In this chapter, we discuss the interplay between these three key elements, reveal how epigenetic modifications may mediate genetic su...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Authors: Ceribelli A, Selmi C Abstract Genomic predisposition fails to fully explain the onset of complex diseases, which is well illustrated by the largely incomplete concordance among monozygotic twins. Epigenetic mechanisms, including DNA methylation, chromatin remodeling, and non-coding RNA, are the link between environmental stimuli and disease onset on a permissive genetic background in autoimmune and chronic inflammatory diseases. Autoimmune diseases now include almost 100 conditions and are estimated to cumulatively affect up to 5% of the world population with a healthcare expenditure superior to cancer wor...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Authors: Zhang L, Lu Q, Chang C Abstract Epigenetic mechanisms, which include DNA methylation, histone modification, and microRNA (miRNA), can produce heritable phenotypic changes without a change in DNA sequence. Disruption of gene expression patterns which are governed by epigenetics can result in autoimmune diseases, cancers, and various other maladies. Mechanisms of epigenetics include DNA methylation (and demethylation), histone modifications, and non-coding RNAs such as microRNAs. Compared to numerous studies that have focused on the field of genetics, research on epigenetics is fairly recent. In contrast to ...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Vitiligo is an autoimmune skin disease presenting with distinct, patchy areas of depigmentation that can appear anywhere on the body. These white patches occur when autoreactive, cytotoxic CD8+ T cells promote elimination of melanocytes, the pigment-producing cells of the epidermis (Frisoli et al. 2020). Vitiligo affects approximately 1% of the global population equally across races and sexes, and frequently presents before the age of 20 (Ta ïeb and Picardo 2009).
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Letters to the Editor Source Type: research
More News: Allergy & Immunology | Autoimmune Disease | Learning | Study | Universities & Medical Training