Artificial intelligence and high-dimensional technologies in the theragnosis of systemic lupus erythematosus

Genetic interrogation for sequence and copy number variants in systemic lupus erythematosus

“…However, the contributions of non-coding variants towards disease have yet to be thoroughly elucidated and the downstream analyses of such intronic regions remain complex and highly challenging ( Zhao et al, 2020 ). As such, WES has become increasingly popular in clinical diagnostics and research due to its utility (∼95% capture of exonic and splice site regions ( Field, 2021 ; Zhang et al, 2021 )), ease of analysis ( Yaung et al, 2023 ) and lower cost (one-third that of WGS ( Goodwin et al, 2016 ; Field, 2021 ))…”

“…Elucidating the pathogenesis of autoimmune diseases like SLE remains complex, and studies have called for the need for a multi-omics approach to furnish our current understanding of the disease ( Fang et al, 2016 ; Hedrich, 2017 ; Kwon et al, 2019 ; Yaung et al, 2023 ). Thus far, transcriptomic signatures obtained from blood and tissues have shown an enrichment of genes involved in the IFN response ( Banchereau et al, 2016 ; Der et al, 2019 ), which corroborates with previous genetic data ( Baechler et al, 2003 ; Reynier et al, 2011 ).…”

“…Sequencing technologies have been fundamental for researchers due to their high-throughput capabilities and more recently, their cost-effectiveness ( Goodwin et al, 2016 ). This has allowed for comprehensive genomic studies (i.e., point mutations, small indels, CNVs) and paved the way for multi-omics studies ( Levy and Myers, 2016 ; Lee et al, 2022 ; Satam et al, 2023 ; Yaung et al, 2023 ). In the context of systemic autoimmune diseases like SLE, multiple susceptibility loci identified by GWAS cumulatively contribute risk towards its development but carry a relatively low disease risk individually ( Sestak et al, 2011 ; Wahren-Herlenius and Dorner, 2013 ).…”

“…And within this patient group, around 3%–10% of patients carry a single disease-causing variant ( Almlof et al, 2019 ; Belot et al, 2020 ; Charras et al, 2023 ), thus being increasingly recognized and termed as monogenic SLE ( Harley and Sawalha, 2022 ; Vinuesa et al, 2023 ). Pinpointing the disease-causing variant will contribute greatly to our current knowledge of lupus pathogenesis, and this can be achieved through the use of next-generation sequencing (NGS) techniques ( Sanger et al, 1977 ; Slatko et al, 2018 ; You et al, 2018 ; Yaung et al, 2023 ). As such, a focused strategy is needed together with prioritizing NGS and research efforts towards cSLE patients ( Mina and Brunner, 2013 ).…”

“…Further diving into genomic studies of SLE through NGS techniques has brought to light the utility of whole exome (WES) and whole genome sequencing (WGS). Our colleagues have also reviewed various technologies that could be employed to elucidate disease mechanisms ( Yaung et al, 2023 ), such as Sanger sequencing ( Sanger et al, 1977 ), single nucleotide polymorphism (SNP) array ( You et al, 2018 ), WES and WGS ( Slatko et al, 2018 ). In this Review, we expound further into the use of NGS techniques, notably WES, across the current genomic landscape of polygenic and monogenic SLE, discussing its potential in reconciling disease risk variants and copy number variations (CNVs) and evaluating the identification of such variants.…”