Rhythm profiling using COFE reveals multi-omic circadian rhythms in human cancers in vivo DOI Creative Commons
Bharath Ananthasubramaniam, Ramji Venkataramanan

PLoS Biology, Год журнала: 2025, Номер 23(5), С. e3003196 - e3003196

Опубликована: Май 27, 2025

The study of ubiquitous circadian rhythms in human physiology requires regular measurements across time. Repeated sampling the different internal tissues that house clocks is both practically and ethically infeasible. Here, we present a novel unsupervised machine learning approach (COFE) can use single high-throughput omics samples (without time labels) from individuals to reconstruct cohorts. COFE simultaneously assign labels identify rhythmic data features used for temporal reconstruction, while also detecting invalid orderings. With COFE, discovered widespread de novo gene expression 11 adenocarcinomas using Cancer Genome Atlas (TCGA) database. arrangement peak times core clock was conserved cancers resembled healthy functional except mistiming few key genes. Moreover, transcriptome were strongly associated with cancer-relevant proteome. genes proteins common all involved metabolism cell cycle. Although these synchronized cycle many cancers, they uncoupled matched tissue. targets most FDA-approved potential anti-cancer drugs tumor tissue amplitudes times. These findings emphasize utility considering “time" cancer therapy, suggest focus on rather than free-running Our thus creates new opportunities repurpose without rhythms.

Язык: Английский

Circadian coupling orchestrates cell growth DOI

Nica Gutu,

Malthe S. Nordentoft,

Marlena Kuhn

и другие.

Nature Physics, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

Язык: Английский

Процитировано

1
Sorption and release of small molecules in PDMS and COC for Organs on chip DOI Creative Commons
Karlis Grindulis,

Nikola Gabriela Matusevica,

Vendija Kozlova

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 23, 2025

Язык: Английский

Процитировано

0
Chronobiologie in der Onkologie: Onkologische Therapien am besten zur individuell optimalen Tageszeit DOI
Carolin Ector, Adrián E. Granada

Deutsches Ärzteblatt, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Процитировано

0
Design, synthesis and in vitro evaluations of new cyclotriphosphazenes as safe drug candidates DOI
Elif Yıldız Gül,

Büşra Tiryaki,

Buse Köse

и другие.

RSC Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Cyclotriphosphazene compounds carrying morpholine, thiomorpholine and triazole groups were synthesized their biological activities investigated. These presented as a class of circadian rhythm-safe drug candidate compounds.

Язык: Английский

Процитировано

0
Circadian clock features define novel subtypes among breast cancer cells and shape drug sensitivity DOI Creative Commons
Carolin Ector, Jeff Didier, Sébastien De Landtsheer

и другие.

Molecular Systems Biology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

Abstract The circadian clock regulates key physiological processes, including cellular responses to DNA damage. Circadian-based therapeutic strategies optimize treatment timing enhance drug efficacy and minimize side effects, offering potential for precision cancer treatment. However, applying these in remains limited due a lack of understanding the clock’s function across types incomplete insights into how affects responses. To address this, we conducted deep phenotyping panel breast cell lines. Observing diverse dynamics, characterized metrics assess rhythm strength stability vitro. This led identification four distinct circadian-based phenotypes among 14 models: functional, weak, unstable, dysfunctional clocks. Furthermore, demonstrate that plays critical role shaping pharmacological various anti-cancer drugs identify features descriptive sensitivity. Collectively, our findings establish foundation implementing cancer, leveraging sensitivity patterns outcomes.

Язык: Английский

Процитировано

0
A combined mathematical and experimental approach reveals the drivers of time-of-day drug sensitivity in human cells DOI Creative Commons

Nica Gutu,

Hitoshi Ishikuma,

Carolin Ector

и другие.

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Март 25, 2025

Abstract The circadian clock plays a pivotal role in regulating various aspects of cancer, influencing tumor growth and treatment responses. There are significant changes drug efficacy adverse effects when drugs administered at different times the day, underscoring importance considering time day treatments. Despite these well-established findings, chronotherapy approaches have yet to fully integrate into clinical practice, largely due stringent requirements for proving safety, alongside need deeper mechanistic insights. In this study, we employ combined mathematical experimental approach systematically investigate factors time-of-day sensitivity human cells. Here show how properties independently shape profiles, providing valuable insights temporal dynamics Understanding fluctuates throughout holds immense potential development personalized strategies aligned with an individual’s internal biological clock, revolutionizing cancer by maximizing therapeutic benefits. Moreover, our framework offers promising avenue refining future screening efforts, paving way more effective targeted therapies across diverse tissue types.

Язык: Английский

Процитировано

0
Rhythm profiling using COFE reveals multi-omic circadian rhythms in human cancers in vivo DOI Creative Commons
Bharath Ananthasubramaniam, Ramji Venkataramanan

PLoS Biology, Год журнала: 2025, Номер 23(5), С. e3003196 - e3003196

Опубликована: Май 27, 2025

The study of ubiquitous circadian rhythms in human physiology requires regular measurements across time. Repeated sampling the different internal tissues that house clocks is both practically and ethically infeasible. Here, we present a novel unsupervised machine learning approach (COFE) can use single high-throughput omics samples (without time labels) from individuals to reconstruct cohorts. COFE simultaneously assign labels identify rhythmic data features used for temporal reconstruction, while also detecting invalid orderings. With COFE, discovered widespread de novo gene expression 11 adenocarcinomas using Cancer Genome Atlas (TCGA) database. arrangement peak times core clock was conserved cancers resembled healthy functional except mistiming few key genes. Moreover, transcriptome were strongly associated with cancer-relevant proteome. genes proteins common all involved metabolism cell cycle. Although these synchronized cycle many cancers, they uncoupled matched tissue. targets most FDA-approved potential anti-cancer drugs tumor tissue amplitudes times. These findings emphasize utility considering “time" cancer therapy, suggest focus on rather than free-running Our thus creates new opportunities repurpose without rhythms.

Язык: Английский

Процитировано

0