Early 2025 preprints – the genetics & genomics edition

Bioinformatics

Decoding the Molecular Language of Proteins with Evolla

Xibin Zhou, Chenchen Han, Yingqi Zhang, Jin Su, Kai Zhuang, Shiyu Jiang, Zichen Yuan, Wei Zheng, Fengyuan Dai, Yuyang Zhou, Yuyang Tao, Dan Wu, Fajie Yuan

https://www.biorxiv.org/content/10.1101/2025.01.05.630192v2

A very interesting preprint that introduces a multimodal protein-language model that deciphers proteins’ molecular mechanisms through natural language dialogue, trained on a corpus of 546 million AI-generated protein-question-answer triples and encompassing 150 billion word tokens.

Picked by: Jawdat Sandakly

From Zhou et al. This image is made available under a CC-BY 4.0 International license.

Epigenetics

Stress-driven emergence of heritable non-genetic drug resistance

Jinglin L. Xie, Sifei Yin, Theodore S. Yang, Kiran Chandrasekher, Luke Hanson, Sang Hu Kim, Lucas Esqueda, Catherine A. Hogan, Niaz Banaei, June L. Round, Kyla S. Ost, Judith Berman, Daniel F. Jarosz

https://www.biorxiv.org/content/10.1101/2024.12.20.629823v1

This preprint describes how transient exposure to an antifungal drug can drive heritable drug resistance via a prion-like non-genetic mechanism.

Picked by: Chee Kiang (Ethan) Ewe

Gene regulation

Characterization of RNA interference in the model cnidarian Nematostella vectensis reveals partial target silencing but lack of small RNA amplification

Yael Admoni, Magda Lewandowska, Reuven Aharoni, Junchao Shi, Xudong Zhang, Qi Chen, Yehu Moran

https://www.biorxiv.org/content/10.1101/2025.01.03.631050v1

The preprint authors show that Cnidaria contains an antiviral RNAi pathway but lacks small RNA amplification as observed in some other organisms like nematodes. This study sheds lights on the evolution of antiviral mechanisms.

Picked by: Chee Kiang (Ethan) Ewe

From Admoni et al. This image is made available under a CC-BY 4.0 International license.

LINE-1 retrotransposons regulate the exit of human pluripotency and early brain development

Anita Adami, Raquel Garza, Patricia Gerdes, Pia A. Johansson, Fereshteh Dorazehi, Symela Koutounidou, Laura Castilla-Vallmanya, Diahann A.M. Atacho, Yogita Sharma, Jenny G. Johansson, Oliver Tam, Agnete Kirkeby, Roger A. Barker, Molly Gale-Hammell, Christopher H. Douse, Johan Jakobsson

https://www.biorxiv.org/content/10.1101/2025.01.17.633315v1

The preprint authors used a combination of genomic approaches coupled with bioinformatics to demonstrate that the long interspersed nuclear element 1 (L1) retrotransposons are wired into gene regulatory networks in human pluripotent stem cells and represent a set of genetic material that contributes to important transcriptional networks in early human development.

Picked by: Jawdat Sandakly

The KRAB-Zinc Finger protein ZKSCAN3 represses enhancers via embedded retrotransposons

Daniel Moore, Eugenia Wong, Charles Arnal, Stefan Schoenfelder, Mikhail Spivakov, Simon Andrews, Maria A. Christophorou

https://www.biorxiv.org/content/10.1101/2025.01.30.635440v1

This amazing preprint demonstrates a role for KZFPs transcription factor in regulating enhancer activity by targeting transposons.

Picked by: Chee Kiang (Ethan) Ewe

Transposable elements drive regulatory and functional innovation of F-box genes

Miguel Vasconcelos Almeida, Zixin Li, Pedro Rebelo-Guiomar, Alexandra Dallaire, Lukáš Fiedler, Jonathan L. Price, Jan Sluka, Xiaodan Liu, Falk Butter, Christian Rödelsperger, Eric A. Miska

https://www.biorxiv.org/content/10.1101/2024.12.17.628972v1

This exciting preprint demonstrates how transposon elements lead to diversity of gene functions especially in large gene families.

Picked by: Chee Kiang (Ethan) Ewe

From Vasconcelos Almeida et al. This image is made available under a CC-BY-NC-ND 4.0 International license.

Genomics

TimeFlies: an snRNA-seq aging clock for the fruit fly head sheds light on sex-biased aging

Nikolai Tennant, Ananya Pavuluri, Kate O’Connor-Giles, Gunjan Singh, Erica Larschan, Ritambhara Singh

https://www.biorxiv.org/content/10.1101/2024.11.25.625273v3

This preprint showcases a newly developed pan-cell-type scRNA-seq aging clock based on explainable deep neural networks that classifies Drosophila melanogaster head age at single-cell resolution with high accuracy.

Picked by: Jawdat Sandakly

From Tennant et al. This image is made available under a CC-BY-NC-ND 4.0 International license.

Decoy-seq unlocks scalable genetic screening for regulatory small noncoding RNAs

Benedict Choi, Sushil Sobti, Larisa M. Soto, Trey Charbonneau, Aiden Sababi, Albertas Navickas, Hamed S. Najafabadi, Hani Goodarzi

https://www.biorxiv.org/content/10.1101/2025.01.25.634869v1.full

The authors introduce a novel approach for high-content single-cell perturbation screening of smRNAs termed Decoy-seq which inhibits the interaction between smRNA transcripts and their cognate interactome through base pairing and stable duplex formation, thereby providing a systematic and rich portrait of their regulatory functions.

Picked by: Jawdat Sandakly

Transcriptomics

A Blueprint of Sex-Specific Neuronal Regulation in the C. elegans Nervous System at Single-Cell Resolution

Rizwanul Haque, Hagar Setty, Ramiro Lorenzo, Gil Stelzer, Ron Rotkopf, Yehuda Salzberg, Gal Goldman, Sandeep Kumar, Shiraz Nir Halber, Andrew M. Leifer, Elad Schneidman, Patrick Laurent, Meital Oren-Suissa

https://www.biorxiv.org/content/10.1101/2024.12.27.630541v1

The preprint authors performed single cell sequencing on male and hermaphrodite C. elegans to gain insights into sexual dimorphism of the brain.

Picked by: Chee Kiang (Ethan) Ewe

Integrating bulk and single cell RNA-seq refines transcriptomic profiles of individual C. elegans neurons

Alec Barrett, Erdem Varol, Alexis Weinreb, Seth R. Taylor, Rebecca M. McWhirter, Cyril Cros, Berta Vidal, Manasa Basaravaju, Abigail Poff, John A. Tipps, Maryam Majeed, Chen Wang, Emily A. Bayer, Molly Reilly, Eviatar Yemini, HaoSheng Sun, Oliver Hobert, David M. Miller III, Marc Hammarlund

https://www.biorxiv.org/content/10.1101/2025.01.26.634951v1

The preprint authors present a strategy to combine the sensitivity of bulk RNA-seq with the specificity of single cell RNA-seq. Here, this approach improves the resolution of gene expression profiling of the C. elegans nervous system.

Picked by: Chee Kiang (Ethan) Ewe

From Barrett et al. This image is made available under a CC-BY-NC-ND 4.0 International license.