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Method: Interpretable phenotype decoding from multicondition sequencing data with ALPINE
- Wei-Hao Lee,
- Lechuan Li,
- Ruth Dannenfelser,
- and Vicky Yao
Genome Res. December 2025 35: 2756-2769; Published in Advance October 22, 2025, doi:10.1101/gr.280566.125
...components. Specifically, a given single-cell sample is often associated with different technical batch effects and phenotypic conditions, which we term ‘guided variables.’ ALPINE jointly optimizes for the decomposition of an input data set into guided and unguided components and includes a built...
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Research: Hydra has mammal-like mutation rates facilitating fast adaptation despite its nonaging phenotype
- Arne Sahm,
- Konstantin Riege,
- Marco Groth,
- Martin Bens,
- Johann Kraus,
- Martin Fischer,
- Hans Kestler,
- Christoph Englert,
- Ralf Schaible,
- Matthias Platzer,
- and Steve Hoffmann
Genome Res. December 2024 34: 2217-2228; Published in Advance December 4, 2024, doi:10.1101/gr.279025.124
...Hydra have highlighted the role of E cells and processes such as apoptosis and autophagy for this nonsenescent phenotype (Sun et al. 2020; Tomczyk et al. 2020). A number of fundamental studies and resources have been published in recent years that examine Hydra from a molecular perspective...
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Resource: Pangenome-genotyped structural variation improves molecular phenotype mapping in cattle
- Alexander S. Leonard,
- Xena M. Mapel,
- and Hubert Pausch
Genome Res. February 2024 34: 300-309; Published in Advance February 14, 2024, doi:10.1101/gr.278267.123
...quantitative trait loci (e/sQTL) are large contributors to phenotypic variability. Achieving sufficient statistical power for e/sQTL mapping requires large cohorts with both genotypes and molecular phenotypes, and so, the genomic variation is often called from short-read alignments, which are unable...
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Method: Large-scale detection and characterization of inter-chromosomal rearrangements in normozoospermic bulls using massive genotype and phenotype data sets
- Jeanlin Jourdain,
- Harmonie Barasc,
- Thomas Faraut,
- Anne Calgaro,
- Nathalie Bonnet,
- Camille Marcuzzo,
- Amandine Suin,
- Anne Barbat,
- Chris Hozé,
- Florian Besnard,
- Sébastien Taussat,
- Cécile Grohs,
- Claire Kuchly,
- Carole Iampietro,
- Cécile Donnadieu,
- Alain Pinton,
- Didier Boichard,
- and Aurélien Capitan
Genome Res. July 6, 2023 ; Published in Advance July 6, 2023, doi:10.1101/gr.277787.123
...: Congenital anomalies, developmental delay (Ohba et al. 2014) BCL2: M: Immune defects driving to premature death (Xiang et al. 2011) 29 11 genes Deleted No deleterious phenotype reported in heterozygous mutant mice CHORDC1 Putative deregulation M: Weight loss, premature death (Di Savino et al. 2015; Dickinson...
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Method: Identification of phenotype-specific networks from paired gene expression–cell shape imaging data
- Charlie George Barker,
- Eirini Petsalaki,
- Girolamo Giudice,
- Julia Sero,
- Emmanuel Nsa Ekpenyong,
- Chris Bakal,
- and Evangelia Petsalaki
Genome Res. April 2022 32: 750-765; Published in Advance February 23, 2022, doi:10.1101/gr.276059.121
..., multivariate phenotypic data, which here has revealed a clearer picture of how signaling regulates cell morphology in breast cancer.The interoperability of this approach is obvious, with any number of continuous variables measured with gene expression able to be correlated with module eigengenes using WGCNA...
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Research: Environmentally induced plasticity of programmed DNA elimination boosts somatic variability in Paramecium tetraurelia
- Valerio Vitali,
- Rebecca Hagen,
- and Francesco Catania
Genome Res. October 2019 29: 1693-1704; Published in Advance September 23, 2019, doi:10.1101/gr.245332.118
...attention as a regulated mechanism of PDE-dependent phenotypic diversification, other sources of somatic variability such as inefficient IES excision could contribute to the emergence of genetic novelties (Catania et al. 2013) or underlie adaptive phenotypic plasticity (Noto and Mochizuki 2017, 2018). DNA...
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Research: Chromatin-sensitive cryptic promoters putatively drive expression of alternative protein isoforms in yeast
- Wu Wei,
- Bianca P. Hennig,
- Jingwen Wang,
- Yujie Zhang,
- Ilaria Piazza,
- Yerma Pareja Sanchez,
- Christophe D. Chabbert,
- Sophie H. Adjalley,
- Lars M. Steinmetz,
- and Vicent Pelechano
Genome Res. December 2019 29: 1974-1984; Published in Advance November 18, 2019, doi:10.1101/gr.243378.118
...drive the expression of alternative isoforms with different posttranscriptional regulation or even encode alternative protein isoforms (Carlson et al. 1983; Cheung et al. 2008; Fournier et al. 2012; Arribere and Gilbert 2013; Pelechano et al. 2013; Gupta et al. 2014; Lycette et al. 2016).To improve...
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Method: Automated interpretable artificial intelligence genomic prediction with AIGP
- Lei Wei,
- Ziqin Jiang,
- Baoliang Fan,
- Yidan Yan,
- Zhenqiang Xu,
- Xiaoxiang Hu,
- and Yuzhe Wang
Genome Res. March 5, 2026 gr.281006.125; Published in Advance March 5, 2026, doi:10.1101/gr.281006.125
...the relationship between the input (genotype) and 76 output (predictive phenotype) because of their “black box” nature (Novakovsky et al. 2023). 77 For genomics researchers, interpretative information, which is often lacking, can be more 78 valuable than predictions themselves because it can provide new insights...
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Research: Landscape of microRNA and target expression variation and covariation in single mouse embryonic stem cells
- Marcel Tarbier,
- Sebastian D. Mackowiak,
- Vaishnovi Sekar,
- Franziska Bonath,
- Etka Yapar,
- Bastian Fromm,
- Omid R. Faridani,
- Inna Biryukova,
- and Marc R. Friedländer
Genome Res. February 2026 36: 291-302; Published in Advance January 12, 2026, doi:10.1101/gr.279914.124
..., variably, and inversely expressed. Some cells have global biases toward specific miRNAs originating from either end of the hairpin precursor, suggesting the presence of unknown regulatory cofactors. We find that microRNAs generally increase variation and covariation of their targets at the RNA level...
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Method: Recovering gene regulatory networks in single-cell multi-omics data with PRISM-GRN
- Wenhao Zhang,
- Lan Cao,
- Xiaoxuan Gu,
- Yongyu Long,
- and Ying Wang
Genome Res. January 2026 36: 142-158; Published in Advance October 9, 2025, doi:10.1101/gr.280757.125
...with TF expression levels and the chromatin accessibility of target genes, these GRNs drive the emergence of diverse cellular phenotypes through complex regulatory mechanisms. Motivated by such established principles of gene expression, we proposed PRISM-GRN, a probabilistic Bayesian model...

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