PBertKla: a protein large language model for predicting human lysine lactylation sites DOI Creative Commons
Hongyan Lai, Dan Luo,

Mi Yang

et al.

BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 6, 2025

Lactylation is a newly discovered type of post-translational modification, primarily occurring on lysine (K) residues both histones and non-histones to exert diverse effects target proteins. Research has shown that lactylation (Kla) modification ubiquitous in different cells participates the determination cell function fate, as well initiation progression various diseases. Precise identification Kla sites fundamental for elucidating their biological functions uncovering application potential. Here, we proposed novel human site predictor (named PBertKla) through curating reliable benchmark dataset with proper sample length sequence identity threshold train protein large language model optimal hyperparameters. Extensive experimental results consistently demonstrated our possessed robust prediction ability, achieving an AUC (area under receiver operating characteristic curve) value over 0.880 independent validation data. Feature visualization analysis further validated effectiveness feature learning representation from sequences. Moreover, benchmarked PBertKla against other cutting-edge models testing sources, highlighting its superiority transferability. All indicated excelled automatic sites, it would advance investigation modifications significance health disease.

Language: Английский

Insight into the roles of lactylation in macrophages: functions and clinical implications DOI

Min Shu,

Dingci Lu,

Ziyi Zhu

et al.

Clinical Science, Journal Year: 2025, Volume and Issue: 139(02), P. 151 - 169

Published: Jan. 1, 2025

Lactylation, a post-translational modification, has been linked to gene transcription regulation through epigenetic modulation in various pathophysiological processes. The lactylation regulatory proteins, known as writers, erasers, and readers, govern their dynamics by adding, removing, recognizing lactyl groups on proteins. Macrophages, cells of the immune system, maintain homeostasis, responding dynamically diverse internal external stimuli. Emerging researches unveil that lactylation, inducing macrophage activation polarization, affects functionality pathological conditions such inflammation, tumor microenvironment, fibrosis. Evidence progressively indicates lactate-driven alterations levels within macrophages can influence pathogenesis numerous diseases. This review aims systematically summarize research progress macrophages, explore its functions mechanisms which contributes pathology different disease phenotypes, propose future directions along with potential diagnostic therapeutic strategies.

Language: Английский

Citations

1
Post‐Translational Modifications of RNA‐Modifying Proteins in Cellular Dynamics and Disease Progression DOI Creative Commons
Yunfan Lin, Pei Lin, Ye Lu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(44)

Published: Oct. 8, 2024

Abstract RNA‐modifying proteins, classified as “writers,” “erasers,” and “readers,” dynamically modulate RNA by adding, removing, or interpreting chemical groups, thereby influencing stability, functionality, interactions. To date, over 170 distinct modifications more than 100 enzymes have been identified, with ongoing research expanding these numbers. Although significant progress has made in understanding modification, the regulatory mechanisms that govern proteins themselves remain insufficiently explored. Post‐translational (PTMs) such phosphorylation, ubiquitination, acetylation are crucial modulating function behavior of proteins. However, full extent PTM influence on their role disease development remains to be fully elucidated. This review addresses gaps offering a comprehensive analysis roles PTMs play regulating Mechanistic insights provided into how alter biological processes, contribute cellular function, drive progression. In addition, current landscape is examined, highlighting therapeutic potential targeting for precision medicine. By advancing networks, this seeks facilitate effective strategies inspire future critical area

Language: Английский

Citations

4
Development of 3-Arylaminothiophenic-2-carboxylic Acid Derivatives as New FTO Inhibitors Showing Potent Antileukemia Activities DOI

Deyan Zhang,

Lu Liu, Ming Li

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 289, P. 117444 - 117444

Published: Feb. 25, 2025

Language: Английский

Citations

0
PBertKla: a protein large language model for predicting human lysine lactylation sites DOI Creative Commons
Hongyan Lai, Dan Luo,

Mi Yang

et al.

BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 6, 2025

Lactylation is a newly discovered type of post-translational modification, primarily occurring on lysine (K) residues both histones and non-histones to exert diverse effects target proteins. Research has shown that lactylation (Kla) modification ubiquitous in different cells participates the determination cell function fate, as well initiation progression various diseases. Precise identification Kla sites fundamental for elucidating their biological functions uncovering application potential. Here, we proposed novel human site predictor (named PBertKla) through curating reliable benchmark dataset with proper sample length sequence identity threshold train protein large language model optimal hyperparameters. Extensive experimental results consistently demonstrated our possessed robust prediction ability, achieving an AUC (area under receiver operating characteristic curve) value over 0.880 independent validation data. Feature visualization analysis further validated effectiveness feature learning representation from sequences. Moreover, benchmarked PBertKla against other cutting-edge models testing sources, highlighting its superiority transferability. All indicated excelled automatic sites, it would advance investigation modifications significance health disease.

Language: Английский

Citations

0