Distinguishing diseases into distinct subtypes is pivotal for accurate study and effective treatment strategies. The Open Targets Platform integrates biomedical, genetic, and biochemical datasets to support disease ontologies, classifications, and potential gene targets. However, many disease annotations remain incomplete, often necessitating extensive expert medical input. This challenge is especially significant for rare and orphan diseases, where resources are limited.

The research introduces a novel machine learning approach to identify diseases with potential subtypes. Utilizing the extensive database of approximately 23,000 diseases documented in the Open Targets Platform, they derived new features to predict diseases with subtypes using direct evidence. Machine learning models were then applied to analyze feature importance and evaluate predictive performance, uncovering both known and novel disease subtypes.

The model achieved an impressive 89.4% ROC Area Under the Receiver Operating Characteristic Curve in identifying known disease subtypes. The integration of pre-trained deep-learning language models further enhanced the model's performance. Notably, the research identified 515 disease candidates predicted to possess previously unannotated subtypes, paving the way for new insights into disease classification.

"This project demonstrates the incredible potential of machine learning in expanding our understanding of complex diseases," said Dan Ofer. "By leveraging advanced models, we can uncover patterns and subtypes that were previously hidden, ultimately contributing to more precise and personalized treatments."

This innovative methodology enables a robust and scalable approach for improving knowledge-based annotations and provides a comprehensive assessment of disease ontology tiers. "We are excited about the potential of our machine learning approach to revolutionize disease classification," said Prof. Michal Linial. "Our findings can significantly contribute to personalized medicine, offering new avenues for therapeutic development."

The research paper titled “Automated annotation of disease subtypes” is now available in Journal of Biomedical Informatics and can be accessed at https://doi.org/10.1016/j.jbi.2024.104650.

Researchers:

Dan Ofer, Michal Linial

Institution:

Department of Biological Chemistry, The Life Science Institute, The Hebrew University of Jerusalem, Israel

The Hebrew University of Jerusalem is Israel's premier academic and research institution. Serving over 23,000 students from 80 countries, the University produces nearly 40% of Israel’s civilian scientific research and has received over 11,000 patents. Faculty and alumni of the Hebrew University have won eight Nobel Prizes and a Fields Medal. For more information about the Hebrew University, please visit http://new.huji.ac.il/en. 

Self-incompatibility (SI) is a widespread biological mechanism in plants having both male and female reproductive organs, that prevents self-fertilization and promotes genetic diversity. Under this mechanism, fertilization relies on the specific recognition between highly diverse proteins: the RNase (female determinant) and the SLF (male determinant). The interaction between these proteins ensures that plants are only compatible with non-self mates, thus maintaining a diverse gene pool.

The new model proposed by Dr. Friedlander and her team represents a significant advancement in understanding the evolutionary dynamics of self-incompatibility proteins. By allowing for promiscuous interactions—where interactions with unfamiliar partners are likely – and for multiple distinct partners per protein, the model aligns more closely with empirical findings than previous models that assumed only one-to-one interactions. This promiscuity enables a flexible interaction pattern between male and female proteins, offering new insights into how these proteins evolve and interact over generations.

"Our research shows that the ability of proteins to engage in promiscuous interactions is crucial for the long-term evolutionary maintenance of self-incompatibility systems," explained Dr. Friedlander. "We propose that the default state of this system is that recognition is likely and an evolutionary pressure is needed to avoid it, in contrast to what was previously thought. This flexibility not only helps in maintaining genetic diversity but also suggests that similar mechanisms could be operating in other biological systems."

The study also reveals how populations of these plants spontaneously organize into distinct compatibility classes, ensuring full compatibility across different classes while maintaining incompatibility within the same class. The model predicts various evolutionary paths that could lead to the formation or elimination of these compatibility classes based solely on point mutations. The dynamic balance between the emergence and decay of these classes, which provides a sustainable model of evolution, was analyzed by the researchers using a mixture of empirical and theoretical tools borrowed from the field of statistical mechanics in physics.

"These insights from our study have profound implications not only for plant biology but also for understanding the fundamental principles of molecular recognition and its impact on the evolution of biological networks," Dr. Friedlander added. "Our findings could also help in the conservation of plant biodiversity."

This research, which highlights the role of promiscuous and multi-partner molecular interactions, is likely to inspire seeking these two elements in additional biological systems, and help in explaining the evolution of various complex molecular networks.

The research paper titled “The role of promiscuous molecular recognition in the evolution of RNase-based self-incompatibility in plants” is now available in Nature Communications and can be accessed at https://doi.org/10.1038/s41467-024-49163-7.

Pictures

Title: A shift of paradigm in the molecular recognition model: from one-to –one (left) into many-to-many (right).

Description: Previous models of self-incompatibility accounted for only one-to-one interactions between male and female-determinant proteins. The new model allows for a more general network of interactions, where each protein can interact with any number of partners.

Credit: Tamar Friedlander and Amit Jangid.

Title: Tamar Friedlander holding two petunias

Credit: Nathan Mengisto, Faculty of Agriculture, HUJI.

Researchers:

Keren Erez¹, Amit Jangid¹, Ohad Noy Feldheim² & Tamar Friedlander¹

Institutions:

1) The Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture, Faculty of Agriculture, The Hebrew University of Jerusalem

2) The Einstein Institute of Mathematics, Faculty of Natural Sciences, The Hebrew University of Jerusalem

The Hebrew University of Jerusalem is Israel's premier academic and research institution. Serving over 23,000 students from 80 countries, the University produces nearly 40% of Israel’s civilian scientific research and has received over 11,000 patents. Faculty and alumni of the Hebrew University have won eight Nobel Prizes and a Fields Medal. For more information about the Hebrew University, please visit http://new.huji.ac.il/en. 

The terror attack by Hamas militants on October 7th, 2023, marked the beginning of a profound national crisis in Israel, leading to widespread trauma and significant mental health challenges across the country. The primary objective of this research was to create a model that can predict the prevalence of PTSD in the aftermath of trauma exposure across different segments of the Israeli population based on their exposure levels to the trauma.

The research team categorized the Israeli population into six distinct groups depending on their exposure to the conflict: direct exposure to terror, close-proximity to terror, involvement of soldiers in combat and support units, intense and moderate exposure to rocket attacks, and communities indirectly affected. Utilizing national databases, the team estimated the size of each group, conducted a literature review to derive PTSD prevalence rates, and performed a random-effects meta-analysis for the prevalence of PTSD in each group.

The findings suggest that approximately 5.3% of the Israeli population, or about 519,923 individuals, may develop PTSD as a result of the terror attack and the conflict, with a prediction interval ranging from 160,346 to 879,502. The study emphasizes the substantial mental health impact of such mass trauma and provides a crucial tool for policymakers, clinicians, and researchers. This model not only facilitates the planning and implementation of necessary mental health interventions but also has the potential to serve as a framework for addressing future mass trauma incidents worldwide.

This predictive model for post-traumatic stress disorder (PTSD) presents a pivotal opportunity for policy action. Following the mass terror attack and subsequent war, proactive measures are imperative. Policy recommendations should prioritize resource allocation for mental health services, including increased funding for counseling, therapy programs, and psychiatric care. As the need across the population is expected to be substantial, there is a pressing need for the adoption of comprehensive, system-wide models facilitating large-scale interventions. Such models should incorporate evidence-based group therapies, short-term individual protocols, initiatives for prevention and early intervention, and the utilization of digital technologies for monitoring and management of mental health symptoms. Governments should invest in training programs for mental health professionals to enhance their ability to identify and treat PTSD effectively. Integrating predictive models into disaster preparedness plans can assist in implementation of mental health interventions following mass trauma events, while global collaboration facilitates knowledge sharing and best practices for addressing mental health needs on a broader scale.

The research paper titled “A Prediction Model of PTSD in the Israeli Population in the Aftermath of October 7th, 2023, Terrorist Attack and the Israel-Hamas War” is now available in medRxiv and can be accessed at https://doi.org/10.1101/2024.02.25.24303235.

Researchers:

Dana Katsoty¹, Michal Greidinger², Yuval Neria^3,4, Aviv Segev^5,6,7, Ido Lurie^5,6

Institutions:

1. Psychology Department, The Hebrew University of Jerusalem, Israel
2. Department of Counseling and Human Development, Faculty of Education, University of Haifa, Israel
3. Department of Psychiatry, Columbia University Irving Medical Center, New York, New York
4. New York State Psychiatric Institute, Columbia University Irving Medical Center, New York
5. Shalvata Mental Health Center, Hod Hasharon, Israel
6. School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Israel
7. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, UK

The Hebrew University of Jerusalem is Israel's premier academic and research institution. Serving over 23,000 students from 80 countries, the University produces nearly 40% of Israel’s civilian scientific research and has received over 11,000 patents. Faculty and alumni of the Hebrew University have won eight Nobel Prizes and a Fields Medal. For more information about the Hebrew University, please visit http://new.huji.ac.il/en. 

(photo credit: DALL-E, AI)

Physiological synchrony refers to the alignment of physiological responses between individuals. This can include parameters like heart rate, respiration, and skin conductance. When two people are physiologically in sync, their bodily functions align in a way that is measurable and often occurs naturally during interactions.

The research integrated both experimental and observational methods to investigate how physiological synchrony influences romantic appeal. An online experiment involving 144 participants demonstrated that inducing synchrony between actors significantly boosted their attractiveness ratings. Further investigations in a lab-based speed-dating scenario with 48 participants identified individuals with a naturally high propensity to synchronize in both social and nonsocial contexts, termed 'Super Synchronizers'. These individuals were consistently rated as more romantically appealing, underscoring the potential of physiological alignment to significantly enhance perceived attractiveness.

Dr. Atzil explains, "Our findings suggest that the ability to synchronize with others might not just be a social skill but could stem from more fundamental sensorimotor abilities that require an individual to adapt themselves to dynamic inputs. This adaptability, whether in response to social cues or rhythmic patterns, is perceived as attractive, potentially because of the beneficial physiological consequences a synchronous partner can have."

The study proposes that synchronized physiological states can improve regulation across various bodily systems, making these interactions more fulfilling. Additionally, effective synchrony may indicate cognitive and evolutionary advantages, suggesting a deeper biological importance of this trait.

Despite these promising insights, Dr. Atzil notes the limitations of the research. "The cross-sectional design of our study limits our ability to draw definitive conclusions about the long-term stability of synchrony as a trait and its causal relationship with romantic attraction," she remarks. Future research will delve into these dynamics more deeply, especially considering the implications of synchrony in sustained romantic relationships and across different sexual orientations.

This study not only advances our understanding of romantic attraction but also paves the way for further exploration into how physiological and behavioral synchrony can shape human relationships in broader contexts.

The research paper titled “Social and nonsocial synchrony are interrelated and romantically attractive” is now available in Communications Psychology and can be accessed at https://doi.org/10.1038/s44271-024-00109-1.

Researchers:

Matan. Cohen, Maayan. Abargil, Merav. Ahissar, Shir Atzil

Institution:

Department of Psychology, Hebrew University of Jerusalem

The Hebrew University of Jerusalem is Israel's premier academic and research institution. Serving over 23,000 students from 80 countries, the University produces nearly 40% of Israel’s civilian scientific research and has received over 11,000 patents. Faculty and alumni of the Hebrew University have won eight Nobel Prizes and a Fields Medal. For more information about the Hebrew University, please visit http://new.huji.ac.il/en. 

Cryogenic damage significantly impacts the potential success of organ preservation, affecting thousands of people worldwide who are in need of organ transplants. Each year, millions of individuals are diagnosed with conditions that could be treated with organ transplants, yet the shortage of viable, preserved organs leaves many on long waiting lists. The inability to effectively preserve organs for extended periods means that a substantial number of organs are discarded due to damage from ice crystal formation and other cryogenic effects. This not only limits the number of transplants that can be performed but also exacerbates the shortage, ultimately impacting the health and survival of countless patients who depend on these life-saving procedures.

Building on the foundation of previous research into ice-binding proteins (IBPs), this groundbreaking study demonstrates how the strategic use of antifreeze proteins (AFPs) can mitigate cryogenic damage and revolutionize organ freezing techniques. Through the strategic deployment of different types of antifreeze proteins, such as AFPIII from fish and TmAFP from larvae of flour beetles, the research team successfully delayed crystallization and influence devitrification even at temperatures below -80 degrees Celsius.

Utilizing a state-of-the-art microscope stage capable of precise temperature control and rapid cooling at a rate of 100 degrees Celsius per second, the study compared samples containing antifreeze proteins with those without. These samples were not frozen to an astonishing -180 degrees Celsius but when thawed gradually some were frozen while other did not. The samples were analysed under a microscope.

"The findings of our research mark a significant step forward in organ preservation technology," explained Dr. Maya Bar Dolev. "By inhibiting crystallization and crystal growth, antifreeze proteins hold immense promise for extending the viability of frozen organs and enabling previously impossible transplants."

Prof. Ido Braslavsky further emphasized the potential impact of this breakthrough: "This advancement opens doors to a new era in tissue preservation and organ transplantation. With further development, we envision longer preservation periods, enhanced quality during transport, and innovative transplant procedures, including complex organ combinations like heart-lung transplants and uterine tissue transplants."

The implications of this research are profound, offering hope for improved organ availability, extended preservation windows, and ultimately, saving countless lives. As the field of tissue preservation embraces the potential of antifreeze proteins, the future of organ transplantation shines brighter than ever before.

The research paper titled “Extended Temperature Range of the Ice-Binding Protein Activity” is now available in Langmuir and can be accessed at https://doi.org/10.1021/acs.langmuir.3c03710.

Researchers:

Vera Sirotinskaya¹, Maya Bar Dolev^1,2, Victor Yashunsky^1,3, Liat Bahari¹, and Ido Braslavsky¹

Institutions:

1) Institute of Biochemistry, Food Science, and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem

2) Faculty of Biotechnology and Food Engineering, Technion

3) The Swiss Institute for Dryland Environmental and Energy Research, Ben Gurion University

The Hebrew University of Jerusalem is Israel's premier academic and research institution. Serving over 23,000 students from 80 countries, the University produces nearly 40% of Israel’s civilian scientific research and has received over 11,000 patents. Faculty and alumni of the Hebrew University have won eight Nobel Prizes and a Fields Medal. For more information about the Hebrew University, please visit http://new.huji.ac.il/en.