Defining characteristics and conservation of poorly annotated genes in Caenorhabditis elegans using WormCat 2.0.
Defining characteristics and conservation of poorly annotated genes in Caenorhabditis elegans using WormCat 2.0.
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DOI：
10.1093/genetics/iyac085
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发表时间：
2022-07-30
期刊：
影响因子：
3.3
通讯作者：
Walker, Amy K.
中科院分区：
文献类型：
--
作者：
Higgins, Daniel P.;Weisman, Caroline M.;Lui, Dominique S.;D'Agostino, Frank A.;Walker, Amy K.
组学工具为生物发现提供了广泛的数据集。然而，在RNA序列、蛋白质组学或GWAS(Genome-Wide Association Study)数据中用于识别重要基因或途径的计算工具依赖于基因本体注释，并且偏向于描述良好的途径。这限制了它们的用途，因为注释不佳的基因可能具有新的功能，但往往被忽略。最近，我们开发了一个针对秀丽线虫基因组数据的注释和类别丰富工具WormCat，它提供了直观的可视化输出。与基于基因本体的丰富工具不同，WormCat 2.0将这些基因保留为一个特殊的未分配类别。在这里，我们表明未分配的基因类别丰富展示了组织特定的表达模式，并可以包括在已发表的数据集中确定的具有生物学功能的基因。注释不佳的基因通常被认为具有潜在的物种特异性，因此降低了生物医学界的兴趣。相反，我们发现大约3%的未分配基因与人类同源，包括一些与人类疾病有关的基因。这些人类同源基因本身几乎没有注释信息。最近开发的一种结合谱系关系的方法(无意义)表明，BLAST未能检测到同源性，这解释了许多未分配基因的明显谱系特异性。这表明一个更大的子集可能与人类基因有关。WormCat提供了一种注释策略，允许将未分配的基因与特定的表型和已知的途径相关联。利用线虫强大的遗传工具在线虫中建立这些关联，为进一步研究和洞察这些未被研究的基因提供了一条途径。
Omics tools provide broad datasets for biological discovery. However, the computational tools for identifying important genes or pathways in RNA-seq, proteomics, or GWAS (Genome-Wide Association Study) data depend on Gene Ontogeny annotations and are biased toward well-described pathways. This limits their utility as poorly annotated genes, which could have novel functions, are often passed over. Recently, we developed an annotation and category enrichment tool for Caenorhabditis elegans genomic data, WormCat, which provides an intuitive visualization output. Unlike Gene Ontogeny-based enrichment tools, which exclude genes with no annotation information, WormCat 2.0 retains these genes as a special UNASSIGNED category. Here, we show that the UNASSIGNED gene category enrichment exhibits tissue-specific expression patterns and can include genes with biological functions identified in published datasets. Poorly annotated genes are often considered to be potentially species-specific and thus, of reduced interest to the biomedical community. Instead, we find that around 3% of the UNASSIGNED genes have human orthologs, including some linked to human diseases. These human orthologs themselves have little annotation information. A recently developed method that incorporates lineage relationships (abSENSE) indicates that the failure of BLAST to detect homology explains the apparent lineage specificity for many UNASSIGNED genes. This suggests that a larger subset could be related to human genes. WormCat provides an annotation strategy that allows the association of UNASSIGNED genes with specific phenotypes and known pathways. Building these associations in C. elegans, with its robust genetic tools, provides a path to further functional study and insight into these understudied genes.
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