Fusion transcript detection using spatial transcriptomics
Fusion transcript detection using spatial transcriptomics
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DOI：
10.1186/s12920-020-00738-5
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发表时间：
2020-08-04
影响因子：
2.7
通讯作者：
Sonnhammer, Erik L. L.
中科院分区：
文献类型：
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作者：
Friedrich, Stefanie;Sonnhammer, Erik L. L.
背景融合转录本参与肿瘤的发生，在肿瘤异质性、肿瘤演变和肿瘤治疗抗性中起着至关重要的作用。然而，由于缺乏具有空间信息的全长转录本，尚未在组织切片中以高空间分辨率研究融合转录本。新的高通量技术，如空间转录组学，几乎在单细胞水平上测量组织切片的转录组。虽然这种技术不允许直接检测融合转录本，我们表明，它们可以推断使用相关的亲本基因的相对聚（A）尾丰度。方法我们提出了一种新的方法STfusion，它利用空间转录组学来推断poly（A）尾的存在和不存在。融合转录物缺少5 '基因的聚腺苷酸尾，而3 '基因的聚腺苷酸尾数目增加。其表达水平由5 '基因的上游启动子决定。STfusion使用新的C评分测量观察到的和预期的poly（A）尾数之间的差异。结果我们验证了STfusion在已知融合的HeLa细胞上预测融合转录本的能力。应用于临床前列腺癌数据的STfusion和C-评分揭示了12个组织切片中几乎具有单细胞分辨率的顺式SAGeSLC 45 A3-ELK 4的空间分布。顺式SAGe发生在疾病区域，例如发炎、前列腺上皮内瘤变或癌性区域，并且偶尔发生在正常腺体中。结论STfusion检测肿瘤细胞系和临床组织中的融合转录本，并区分由反式剪接事件引起的嵌合体转录本。通过STfusion和使用C-评分，融合转录物可以在几乎单细胞水平上在临床组织切片中空间定位。
Background Fusion transcripts are involved in tumourigenesis and play a crucial role in tumour heterogeneity, tumour evolution and cancer treatment resistance. However, fusion transcripts have not been studied at high spatial resolution in tissue sections due to the lack of full-length transcripts with spatial information. New high-throughput technologies like spatial transcriptomics measure the transcriptome of tissue sections on almost single-cell level. While this technique does not allow for direct detection of fusion transcripts, we show that they can be inferred using the relative poly(A) tail abundance of the involved parental genes. Method We present a new method STfusion, which uses spatial transcriptomics to infer the presence and absence of poly(A) tails. A fusion transcript lacks a poly(A) tail for the 5 ' gene and has an elevated number of poly(A) tails for the 3 ' gene. Its expression level is defined by the upstream promoter of the 5 ' gene. STfusion measures the difference between the observed and expected number of poly(A) tails with a novel C-score. Results We verified the STfusion ability to predict fusion transcripts on HeLa cells with known fusions. STfusion and C-score applied to clinical prostate cancer data revealed the spatial distribution of the cis-SAGeSLC45A3-ELK4in 12 tissue sections with almost single-cell resolution. The cis-SAGe occurred in disease areas, e.g. inflamed, prostatic intraepithelial neoplastic, or cancerous areas, and occasionally in normal glands. Conclusions STfusion detects fusion transcripts in cancer cell line and clinical tissue data, and distinguishes chimeric transcripts from chimeras caused by trans-splicing events. With STfusion and the use of C-scores, fusion transcripts can be spatially localised in clinical tissue sections on almost single cell level.