Jul 2025

• Advisory Board and Contents

TrendsTalk

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  The Genomics Preprint Club: rethinking peer review through community and dialogue

  • Judit García-González,
  • Lathan Liou

  Journal clubs have long served as forums for discussing recent articles in the literature. However, the aims and structures of these clubs are evolving, particularly with the surge in the popularity of preprints and advances in virtual meeting platforms. In 2024, Judit García-González and Lathan Liou co-founded The Genomics Preprint Club ( www.genomicspreprints.com ), which enables early career researchers (ECRs) to critically evaluate preprints in the field of genomics with colleagues from other institutions.

Spotlights

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  Toward equitable biomarkers of aging: rethinking methylation clocks

  • Selina Wu,
  • Gita A. Pathak,
  • Zhangying Chen

  DNA methylation clocks, which measure biological age by analyzing age-related DNA methylation patterns, offer powerful biomarkers of aging. But as a recent preprint highlights, current models underperform in diverse populations. The next generation of clocks must prioritize equity to avoid reinforcing disparities in precision aging and disease risk prediction.
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  Moving towards sequencing-based metabolomics

  • Alia Clark-ElSayed,
  • Andrew D. Ellington,
  • Edward M. Marcotte

  Metabolites are chemically heterogeneous and difficult to quantify in easily read formats. Recently, Tan and Fraser demonstrated that metabolites can be readily quantified by pairing aptamer function with DNA sequencing. This reflects a larger trend of sequencing for assessing biomolecule abundances, further leading to sequencing being a universal analytical tool.

Forum

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  RNA methylation in retrotransposon control

  • Basil Barter,
  • Jungnam Cho

  Open Access

  N6-methyladenosine (m6A) regulates retrotransposon activity, shifting between repression and activation across different species and developmental stages. It promotes RNA decay, sequestration, or stability, influencing genome integrity, adaptation, and disease. This article explores the dual role of m6A in retrotransposon control, highlighting its evolutionary significance in genome regulation and cellular differentiation.

Opinion

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  Can genomic analysis actually estimate past population size?

  • Janeesh K. Bansal,
  • Richard A. Nichols

  Open Access

  Genomic data can be used to reconstruct population size over thousands of generations, using a new class of algorithms [sequentially Markovian coalescent (SMC) methods]. These analyses often show a recent decline in $N_{\mathrm{e}}$ (effective size), which at face value implies a conservation or demographic crisis: a population crash and loss of genetic diversity. This interpretation is frequently mistaken. Here we outline how SMC methods work, why they generate this misleading signal, and suggest simple approaches for exploiting the rich information produced by these algorithms. In most species, genomic patterns reflect major changes in the species’ range and subdivision over tens or hundreds of thousands of years. Consequently, collaboration between geneticists, palaeoecologists, palaeoclimatologists, and geologists is crucial for evaluating the outputs of SMC algorithms.

Reviews

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  Dynamics of replication timing during mammalian development

  • Tsunetoshi Nakatani

  Open Access

  Recent developments in low-input genomics techniques have greatly advanced the analysis of the order in which DNA is replicated in the genome – that is, replication timing (RT) – and its interrelationships with other processes. RT correlates or anticorrelates with genomic-specific parameters such as gene expression, chromatin accessibility, histone modifications, and the 3D structure of the genome, but the significance of how they influence each other and how they relate to biological processes remains unclear. In this review I discuss the results of recent analyses of RT, the time at which it is remodeled and consolidated during embryogenesis, how it influences development and differentiation, and the regulatory mechanisms and factors involved.
• Featured Article
  

  Advances in understanding LINE-1 regulation and function in the human genome

  • Xiufeng Li,
  • Nian Liu

  LINE-1 (long interspersed nuclear element 1, L1) retrotransposons constitute ~17% of human DNA (~0.5 million genomic L1 copies) and exhibit context-dependent expression in different cell lines. Recent studies reveal that L1 is under multilayered control by diverse factors that either collaborate or compete with each other to ensure precise L1 activity. Remarkably, L1s have been co-opted as various transcription-dependent regulatory elements, such as promoters, enhancers, and topologically associating domain (TAD) boundaries, that regulate gene expression in zygotic genome activation, aging, cancer, and other disorders. This review highlights the regulation of L1 and its regulatory functions that influence disease and development.
• Featured Article
  

  The origins and evolution of translation factors

  • Evrim Fer,
  • Tony Yao,
  • Kaitlyn M. McGrath,
  • Aaron D. Goldman,
  • Betül Kaçar

  Translation is an ancient molecular information processing system found in all living organisms. Over the past decade, significant progress has been made in uncovering the origins of early translation. Yet, the evolution of translation factors – key regulators of protein synthesis – remains poorly understood. This review synthesizes recent findings on translation factors, highlighting their structural diversity, evolutionary history, and organism-specific adaptations across the tree of life. We examine conserved translation factors, their coevolution, and their roles in different steps in translation: initiation, elongation, and termination. The early evolution of translation factors serves as a natural link between modern genetics and the origins of life. Traditionally rooted in chemistry and geology, incorporating evolutionary molecular biology into the studies of life’s emergence provides a complementary perspective on this complex question.
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  Chromatin accessibility provides a window into the genetic etiology of human brain disease

  • Jaroslav Bendl,
  • John F. Fullard,
  • Kiran Girdhar,
  • Pengfei Dong,
  • Roman Kosoy,
  • Biao Zeng,
  • Gabriel E. Hoffman,
  • Panos Roussos

  Neuropsychiatric and neurodegenerative diseases have a significant genetic component. Risk variants often affect the noncoding genome, altering cis-regulatory elements (CREs) and chromatin structure, ultimately impacting gene expression. Chromatin accessibility profiling methods, especially assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), have been used to pinpoint disease-associated SNPs and link them to affected genes and cell types in the brain. The integration of single-cell technologies with genome-wide association studies (GWAS) and transcriptomic data has further advanced our understanding of cell-specific chromatin dynamics. This review discusses recent findings regarding the role played by chromatin accessibility in brain disease, highlighting the need for high-quality data and rigorous computational tools. Future directions include spatial chromatin studies and CRISPR-based functional validation to bridge genetic discovery and clinical applications, paving the way for targeted gene-regulatory therapies.
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  Functional genomic perspectives on plant terrestrialization

  • Cäcilia F. Kunz,
  • Elisa S. Goldbecker,
  • Jan de Vries

  Open Access

  Plant evolutionary research has made leaps in exploring the deep evolutionary roots of embryophytes. A solid phylogenomic framework was established, allowing evolutionary inferences. Comparative genomic approaches revealed that many genes coding for transcription factors, morphogenetic regulators, specialized metabolic enzymes, phytohormone signaling, and more are not innovations of land plants but have a deep streptophyte algal ancestry. Are these just spurious homologs, or do they actualize traits we deem important in embryophytes? Building on streptophyte algae genome data, current endeavors delve into the functional significance of whole cohorts of homologs by leveraging the power of comparative high-throughput approaches. This ushered in the identification of recurrent themes in function, ultimately providing a functional genomic definition for the toolkit of plant terrestrialization.

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