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Microarray to deep sequencing: transcriptome and miRNA profiling to elucidate molecular pathways in systemic lupus erythematosus

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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical manifestations and autoantibody repertoires. The etiology of SLE is multifactorial involving genetic, epigenetic and environmental factors. This complexity leads to poor prognosis, which poses major challenges in the treatment of SLE. Understanding the complex genetic pathways and regulatory mechanisms operative in SLE was feasible by utilizing several highly efficient molecular biological tools during the past few years. In this perspective, DNA microarray technology offered a high-throughput platform in unraveling SLE-associated genes. Additionally, extensive microarray analysis had demonstrated aberrant DNA methylation pattern and differential microRNAs, thus contributing to the knowledge of epigenetic modulators and posttranscriptional regulatory machinery in SLE. It was through the aid of these technologies that interferon signature was identified as an important contributor in SLE pathogenesis along with dysregulation of cytokine-, chemokine- and apoptosis-related genes. The emergence of next-generation sequencing technologies such as RNA sequencing has added new dimensions in understanding the dynamics of the disease processes. Compared with microarrays, deep sequencing has provided higher resolution in gene expression measurement along with identification of different splicing events, noncoding RNAs and novel loci in SLE. The focus, therefore, has now been shifted toward the identification of novel gene loci and their isoforms, and their implication in disease pathogenesis. This advancement in the technology from microarray to deep sequencing has helped in deciphering the molecular pathways involved in pathogenesis of SLE and opens new avenues to develop novel treatment strategies for SLE.

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Acknowledgments

The authors acknowledge and thank the Department of Biotechnology, New Delhi, India (BT/PR4619/MED/30/834/2012), for financial assistance to Geeta Rai and the Council of Scientific and Industrial Research (CSIR), New Delhi, India, for a research fellowship to Richa Rai.

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Rai, G., Rai, R., Saeidian, A.H. et al. Microarray to deep sequencing: transcriptome and miRNA profiling to elucidate molecular pathways in systemic lupus erythematosus. Immunol Res 64, 14–24 (2016). https://doi.org/10.1007/s12026-015-8672-y

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