Peripheral blood biomarkers in Friedreich's ataxia

The identification of biomarkers for Friedreich’s ataxia (FRDA), a rare and debilitating recessive Mendelian neurodegenerative disorder, is an important goal for disease follow-up and assessment of treatments. Clinical scales are not sensitive enough to detect small, short-term changes that may be indicative of treatment effectiveness. We used differential expression, correlation with expansion size, network analysis, machine learning, and enrichment analysis to identify gene expression biomarkers which differentiated FRDA patients from both heterozygous expansion carriers and controls (821 individuals in total), resulting in a disease signature for FRDA. Our 27-gene expression panel includes genes which are linked to inflammation, lipid metabolism and apoptosis, and overlaps with previous studies and a with a novel mouse model for FRDA. Future studies should seek to expand the search for FRDA biomarkers to include changes in epigenetic regulation and protein expression. 1299 peripheral blood samples, of which 733 were used in study. 4 samples were run twice, but were not intended as technical replicates. Sample status is indicates by characteristics: sample column and can be either patient, heterozygous carrier or control

弗里德赖希共济失调（Friedreich’s ataxia, FRDA）是一种罕见且可导致残疾的隐性孟德尔型神经退行性疾病，识别其生物标志物是疾病随访与治疗效果评估的重要目标。当前临床量表无法灵敏检测出可能提示治疗有效性的微小短期变化。本研究通过差异表达分析、扩增片段大小相关性分析、网络分析、机器学习及富集分析，对共计821名受试者的样本进行分析，筛选出可区分弗里德赖希共济失调患者、杂合扩增携带者与健康对照的基因表达生物标志物，构建了该病的特征基因表达谱。本研究得到的27基因表达特征组涵盖了与炎症、脂质代谢及细胞凋亡相关的基因，且与既往研究及一种新型弗里德赖希共济失调小鼠模型存在重叠。未来的相关研究可将弗里德赖希共济失调生物标志物的搜索范围拓展至表观遗传调控与蛋白质表达变化领域。本研究共收集1299份外周血样本，其中733份纳入本次研究。另有4份样本被重复上机检测，但未被用作技术重复样本。样本状态通过样本列中的特征进行标注，可分为患者、杂合携带者或健康对照三类。