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. 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. 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-SAGe SLC45A3-ELK4 in 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. 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.

中文翻译：

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使用空间转录组学进行融合转录本检测。

融合转录物参与肿瘤发生，并且在肿瘤异质性，肿瘤进化和癌症治疗抗性中起关键作用。然而，由于缺乏具有空间信息的全长转录本，因此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，例如空间转录组学，几乎可以在单细胞水平上测量组织切片的转录组。虽然此技术不允许直接检测融合转录本，但我们表明可以使用涉及的亲本基因的相对poly（A）尾部丰度来推断它们。我们提出了一种新的方法STfusion，它使用空间转录组学来推断poly（A）尾部的存在与否。融合转录物缺少5'基因的poly（A）尾，而3'基因的poly（A）尾却数量增加。其表达水平由5'基因的上游启动子定义。STfusion用新颖的C分数测量观察到的和预期的poly（A）尾巴数量之间的差异。我们验证了STfusion能够预测HeLa细胞与已知融合蛋白的融合转录本的能力。STfusion和C评分应用于临床前列腺癌数据揭示了顺式SAGe SLC45A3-ELK4在几乎单细胞分辨率的12个组织切片中的空间分布。顺式SAGe发生在疾病区域，例如发炎，前列腺上皮内瘤变或癌变区域，偶尔在正常腺体中。STfusion可检测癌细胞系和临床组织数据中的融合转录本，并将嵌合转录物与反式剪接事件引起的嵌合体区分开来。通过STfusion和C分数的使用，融合转录本可以在几乎单个细胞水平上空间定位在临床组织切片中。