ヒト転写因子データの未測定範囲を体系化し研究戦略を提示

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2025-09-30 筑波大学

筑波大学と理化学研究所などの研究チームは、ヒト転写因子のChIP-seqデータを網羅的に解析し、膵臓・筋肉・胎盤などで80%以上が未測定であることを明らかにした。血球系では比較的測定が進んでいたが、全体として大きな研究空白が存在する。さらに未測定の転写因子も多数の遺伝子発現に影響し得ることが示され、既存データだけでは遺伝子調節ネットワークを十分に把握できないことが判明。シミュレーション解析により、測定順序を工夫して多様な転写因子を早期に測定する戦略が、疾患関連変異の理解を効率的に改善することが示唆された。本成果は、研究資源の優先配分を考える上で指針を与えるもので、『Briefings in Functional Genomics』に掲載された。

ヒト転写因子データの未測定範囲を体系化し研究戦略を提示
図 本研究で⾏った未測定転写因⼦-組織・細胞型ペアの抽出と戦略的活⽤の概要

<関連情報>

未測定のヒト転写因子ChIP-seqデータが機能ゲノム学に与える影響と戦略的優先順位付けの必要性 Unmeasured human transcription factor ChIP-seq data shape functional genomics and demand strategic prioritization

Saeko Tahara, Haruka Ozaki
Briefings in Functional Genomics  Published::30 September 2025
DOI:https://doi.org/10.1093/bfgp/elaf016

Abstract

Transcription factor (TF) chromatin immunoprecipitation followed by sequencing (ChIP-seq) is essential for identifying genome-wide TF-binding sites (TFBSs), and the collected datasets offer a variety of opportunities for downstream analyses such as inference of gene regulatory network and prediction for effects of single-nucleotide polymorphisms (SNPs) on TFBSs. Although TF ChIP-seq data continue to accumulate in public databases, comprehensive coverage of biologically relevant TF-sample pairs (i.e. combination of targeted TF and cell type) remains elusive. This is due to the need for TF-specific antibodies and large cell numbers, limiting feasible TF–cell type combinations. Moreover, ChIP-seq is measurable when the TF is expressed in the target cell type. Thus, defining the full space of biologically relevant TF–sample pairs—including both measured and unmeasured—is essential to assess and improve dataset comprehensiveness. Here, we investigated publicly available human TF ChIP-seq datasets and introduced the concept of unmeasured TF-sample pairs, defined as biologically relevant TF–sample combinations for which ChIP-seq experiments have not yet been performed. Notably, many expressed TFs in specific cell types remain unmeasured by ChIP-seq, affecting the coverage of regulatory regions revealed by TF ChIP-seq and genome-wide association study–SNP analyses. Furthermore, we propose practical strategies to efficiently supplement currently unmeasured data and discuss how these approaches can significantly enhance data-driven research. The database of unmeasured human TF–sample pairs is publicly accessible at https://moccs-db.shinyapps.io/Unmeasured_shiny_v1/, facilitating the systematic expansion of TF ChIP-seq datasets and thereby enhancing our comprehension of gene regulatory mechanisms.

細胞遺伝子工学
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