Aging is a highly complex and heterogeneous process that progresses at different rates across individuals, making biological age (BA) a more accurate indicator of physiological decline than chronological age. While previous studies have built aging clocks using single-omics data, they often fail to capture the full molecular complexity of human aging. In this work, we leveraged the Human Phenotype Project, a large-scale cohort of 10,000 adults aged 40-70 years, with extensive longitudinal profiling that includes clinical, behavioral, environmental, and multi-omics datasets spanning transcriptomics, lipidomics, metabolomics, and the microbiome. By employing advanced machine learning frameworks capable of modeling nonlinear biological dynamics, we developed and rigorously validated a multi-omics aging clock that robustly predicts diverse health outcomes and future disease risk. Unsupervised clustering of the integrated molecular profiles from multi-omics uncovered distinct biological subtypes of aging, revealing striking heterogeneity in aging trajectories and pinpointing pathway-specific alterations associated with different aging patterns. These findings demonstrate the power of multi-omics integration to decode the molecular landscape of aging and lay the groundwork for personalized healthspan monitoring and precision strategies to prevent age-related diseases.

Histopathology remains the gold standard for cancer diagnosis and prognosis. With the advent of transcriptome profiling, multi-modal learning combining transcriptomics with histology offers more comprehensive information. However, existing multi-modal approaches are challenged by intrinsic multi-modal heterogeneity, insufficient multi-scale integration, and reliance on paired data, restricting clinical applicability. To address these challenges, we propose a disentangled multi-modal framework with four contributions: 1) To mitigate multi-modal heterogeneity, we decompose WSIs and transcriptomes into tumor and microenvironment subspaces using a disentangled multi-modal fusion module, and introduce a confidence-guided gradient coordination strategy to balance subspace optimization. 2) To enhance multi-scale integration, we propose an inter-magnification gene-expression consistency strategy that aligns transcriptomic signals across WSI magnifications. 3) To reduce dependency on paired data, we propose a subspace knowledge distillation strategy enabling transcriptome-agnostic inference through a WSI-only student model. 4) To improve inference efficiency, we propose an informative token aggregation module that suppresses WSI redundancy while preserving subspace semantics. Extensive experiments on cancer diagnosis, prognosis, and survival prediction demonstrate our superiority over state-of-the-art methods across multiple settings. Code is available at https://github.com/helenypzhang/Disentangled-Multimodal-Learning.

RNA sequencing techniques, like bulk RNA-seq and Single Cell (sc) RNA-seq, are critical tools for the biologist looking to analyze the genetic activity/transcriptome of a tissue or cell during an experimental procedure. Platforms like Illumina's next-generation sequencing (NGS) are used to produce the raw data for this experimental procedure. This raw FASTQ data must then be prepared via a complex series of data manipulations by bioinformaticians. This process currently takes place on an unwieldy textual user interface like a terminal/command line that requires the user to install and import multiple program packages, preventing the untrained biologist from initiating data analysis. Open-source platforms like Galaxy have produced a more user-friendly pipeline, yet the visual interface remains cluttered and highly technical, remaining uninviting for the natural scientist. To address this, SeqMate is a user-friendly tool that allows for one-click analytics by utilizing the power of a large language model (LLM) to automate both data preparation and analysis (differential expression, trajectory analysis, etc). Furthermore, by utilizing the power of generative AI, SeqMate is also capable of analyzing such findings and producing written reports of upregulated/downregulated/user-prompted genes with sources cited from known repositories like PubMed, PDB, and Uniprot.

Science and medicine are becoming increasingly digital. Analyzing the resulting volumes of information -- known as "big data" -- is considered a key to better treatment options. "Medical research data are a treasure. They can play a decisive role in developing personalized therapies that are tailored to each individual more precisely than conventional treatments," said Joachim Schultze, Director of Systems Medicine at the DZNE and professor at the Life & Medical Sciences Institute (LIMES) at the University of Bonn. "It's critical for science to be able to use such data as comprehensively and from as many sources as possible."

Following a similar principle--called "swarm learning"--an international research team has trained artificial intelligence algorithms to detect blood cancer, lung diseases and COVID-19 in data stored in a decentralized fashion. This approach has advantage over conventional methods since it inherently provides privacy preservation technologies, which facilitates cross-site analysis of scientific data. Swarm learning could thus significantly promote and accelerate collaboration and information exchange in research, especially in the field of medicine. Experts from the DZNE, the University of Bonn, the information technology company Hewlett Packard Enterprise (HPE) and other research institutions report on this in the scientific journal Nature. Science and medicine are becoming increasingly digital.

We each developed from a single cell—a fertilized egg—that divided and divided and eventually gave rise to the trillions of cells, of hundreds of types, that constitute the tissues and organs of our adult bodies. Advancing our understanding of the molecular programs underlying the emergence and differentiation of these diverse cell types is of fundamental interest and will affect almost every aspect of biology and medicine. Recently, technological advances have made it possible to directly measure the gene expression patterns of individual cells ([ 1 ][1]). Such methods can be used to clarify cell types and to determine the developmental stage of individual cells ([ 2 ][2]). Single-cell transcriptional profiling of successive developmental stages has the potential to be particularly informative, as the data can be used to reconstruct developmental processes, as well as characterize the underlying genetic programs ([ 3 ][3], [ 4 ][4]). ![Figure][5] A genomic technique for tracking cellular development High-throughput single-cell genomic methods enable a global view of cell type diversifcation by transcriptome and epigenome CREDIT: N. DESAI/ SCIENCE FROM CAO ET AL. ([7][6]) AND BIORENDER When I began my doctoral studies in Jay Shendure's lab at the University of Washington, available single-cell sequencing techniques relied on the isolation of individual cells within physical compartments and thus were limited in terms of both throughput and cost. As a graduate student, I developed four high-throughput single-cell genomic techniques to overcome these limitations ([ 5 ][7]–[ 8 ][8]). Leveraging these methods, I profiled millions of single-cell transcriptomes from organisms, in species that included worms, mice, and humans. By quantifying the dynamics of embryonic development at single-cell resolution, I was able to map out the global genetic programs that control cell proliferation and differentiation at the whole-organism scale. By the 1980s, biologists had documented every developmental step in the nematode Caenorhabditis elegans , from a single-cell embryo to the adult worm, and mapped the connections of all of the worm's neurons ([ 9 ][9]). However, although the nematode worm has a relatively small cell number (558 cells at hatching), a comprehensive understanding of the molecular basis for the specification of these cell types remains difficult. To resolve cellular heterogeneity, I first developed a method to specifically label the transcriptomes of large numbers of single cells, which we called sci-RNA-seq (single-cell combinatorial indexing RNA sequencing) ([ 5 ][7]). This method is based on combinatorial indexing, a strategy using split-pool barcoding of nucleic acids to label vast numbers of single cells within a single experiment ([ 9 ][9]). In this study, I profiled nearly 50,000 cells from C. elegans at the L2 stage, which is more than 50-fold “shotgun cellular coverage” of its somatic cell composition. We further defined consensus expression profiles for 27 cell types and identified rare neuronal cell types corresponding to as few as one or two cells in the L2 worm. This was the first study to show that single-cell transcriptional profiling is sufficient to separate all major cell types from an entire animal. C. elegans development follows a tightly controlled genetic program. Other multicellular organisms, such as mice and humans, have much more developmental flexibility. However, conventional approaches for mammalian single-cell profiling lack the throughput and resolution to obtain a global view of the molecular states and trajectories of the rapidly diversifying and expanding cell types. To investigate cell state dynamics in mammalian development, I developed an even more scalable single-cell profiling technique, sci-RNA-seq3 ([ 7 ][6]), and used it to trace the development path of 2 million mouse cells as they traversed diverse paths in a 4-day window of development corresponding to organogenesis (embryonic day 9.5 to embryonic day 13.5). From these data, we characterized the dynamics of cell proliferation and key regulators for each cell lineage, a potentially foundational resource for understanding how the hundreds of cell types forming a mammalian body are generated in development. This was, and remains, the largest publicly available single-cell transcriptional dataset. The sci-RNA-seq3 method enabled this dataset to be generated rapidly, within a few weeks, by a single individual. A major challenge regarding current single-cell assays is that nearly all such methods capture just one aspect of cellular biology (typically mRNA expression), limiting the ability to relate different components to one another and to infer causal relationships. Another technique that I developed, sci-CAR (single-cell combinatorial indexing chromatin accessibility and mRNA) ([ 6 ][10]), was created with the goal of overcoming this limitation, allowing the user to jointly profile the epigenome (chromatin accessibility) and transcriptome (mRNA). I applied sci-CAR to the mouse whole kidneys, recovering all major cell types and linking cis-regulatory sites to their target genes on the basis of the covariance of chromatin accessibility and transcription across large numbers of single cells. To further explore the gene regulatory mechanisms, I invented sci-fate ([ 8 ][8]), a new method that identifies the temporal dynamics of transcription by distinguishing newly synthesized mRNA transcripts from “older” mRNA transcripts in thousands of individual cells. Applying the strategy to cancer cell state dynamics in response to glucocorticoids, we were able to link transcription factors (TFs) with their target genes on the basis of the covariance between TF expression and the amount of newly synthesized RNA across thousands of cells. In summary, my dissertation involved developing the technical framework for quantifying gene expression and chromatin dynamics across thousands to millions of single cells and applying these technologies to profile complex, developing organisms. The methods that I developed enable such projects to be achievable by a single individual, rather than requiring large consortia. Looking ahead, I anticipate that the integration of single-cell views of the transcriptome, epigenome, proteome, and spatial-temporal information throughout development will enable an increasingly complete view of how life is formed. GRAND PRIZE WINNER Junyue Cao Junyue Cao received his undergraduate degree from Peking University and a Ph.D. from the University of Washington. After completing his postdoctoral fellowship at the University of Washington, Junyue Cao started his lab as an assistant professor and lab head of single-cell genomics and population dynamics at the Rockefeller University in 2020. His current research focuses on studying how a cell population in our body maintains homeostasis by developing genomic techniques to profile and perturb cell dynamics at single-cell resolution. CATEGORY WINNER: ECOLOGY AND EVOLUTION Orsi Decker Orsi Decker completed her undergraduate degree at Eötvös Loránd University in Budapest, Hungary. She went on to receive her master's degree in Ecology and Evolution at the University of Amsterdam. Decker completed her doctoral research at La Trobe University in Melbourne, Australia, where she investigated the extinctions of native digging mammals and their context-dependent impacts on soil processes. She is currently a postdoctoral researcher at La Trobe University, where she is examining how land restoration efforts could be improved to regain soil functions through the introduction of soil fauna to degraded areas. [www.sciencemag.org/content/370/6519/925.1][11] CATEGORY WINNER: MOLECULAR MEDICINE Dasha Nelidova Dasha Nelidova completed her undergraduate degrees at the University of Auckland, New Zealand. She completed her Ph.D. in neurobiology at the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland. Nelidova is currently a postdoctoral researcher at the Institute of Molecular and Clinical Ophthalmology Basel, where she is working to develop new translational technologies for treating retinal diseases that lead to blindness. [www.sciencemag.org/content/370/6519/925.2][12] CATEGORY WINNER: CELL AND MOLECULAR BIOLOGY William E. Allen William E. Allen received his undergraduate degree from Brown University in 2012, M.Phil. in Computational Biology from the University of Cambridge in 2013, and Ph.D. in Neurosciences from Stanford University in 2019. At Stanford, he worked to develop new tools for the large-scale characterization of neural circuit structure and function, which he applied to understand the neural basis of thirst. After completing his Ph.D., William started as an independent Junior Fellow in the Society of Fellows at Harvard University, where he is developing and applying new approaches to map mammalian brain function and dysfunction over an animal's life span. [www.sciencemag.org/content/370/6519/925.3][13] 1. [↵][14]1. D. Ramsköld et al ., Nat. Biotechnol. 30, 777 (2012). [OpenUrl][15][CrossRef][16][PubMed][17] 2. [↵][18]1. C. Trapnell , Genome Res. 25, 1491 (2015). [OpenUrl][19][Abstract/FREE Full Text][20] 3. [↵][21]1. D. E. Wagner et al ., Science 360, 981 (2018). [OpenUrl][22][Abstract/FREE Full Text][23] 4. [↵][24]1. K. Davie et al ., Cell 174, 982 (2018). [OpenUrl][25][CrossRef][26][PubMed][27] 5. [↵][28]1. J. Cao et al ., Science 357, 661 (2017). [OpenUrl][29][Abstract/FREE Full Text][30] 6. [↵][31]1. J. Cao et al ., Science 361, 1380 (2018). [OpenUrl][32][Abstract/FREE Full Text][33] 7. [↵][34]1. J. Cao et al ., Nature 566, 496 (2019). [OpenUrl][35][CrossRef][36][PubMed][37] 8. [↵][38]1. J. Cao, 2. W. Zhou, 3. F. Steemers, 4. C. Trapnell, 5. J. Shendure , Nat. Biotechnol. 38, 980 (2020). [OpenUrl][39][CrossRef][40][PubMed][41] 9. [↵][42]1. D. A. Cusanovich et al ., Science 348, 910 (2015). 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Artificial intelligence is a much-discussed topic in medicine, especially in the field of diagnostics. "We aimed to investigate the potential on the basis of a specific example," explains Prof. Joachim Schultze, a research group leader at the DZNE and head of the Department for Genomics and Immunoregulation at the LIMES Institute of the University of Bonn. "Because this requires large amounts of data, we evaluated data on the gene activity of blood cells. Numerous studies have been carried out on this topic and the results are available through databases. Thus, there is an enormous data pool. We have collected virtually everything that is currently available."

In the largest metastudy to date on acute myeloid leukemia, German researchers contend that they have demonstrated that artificial intelligence can detect this common and deadly form of blood cancer. Results of their proof-of-concept study, published in the journal iScience, are based on the analysis of the gene activity of cells found in blood using 12,029 samples from 105 different studies. "Our results support the notion that transcriptomics combined with machine learning could be used as part of an integrated -omics approach where risk prediction, differential diagnosis and subclassification of AML is achieved by genomics while diagnosis could be assisted by transcriptomic-based machine learning," state the study's authors. "The transcriptome holds important information about the condition of cells," says Joachim Schultze, a research group leader at the DZNE and head of the Department for Genomics and Immunoregulation at the LIMES Institute of the University of Bonn. "However, classical diagnostics is based on different data. We therefore wanted to find out what an analysis of the transcriptome can achieve using artificial intelligence--that is to say trainable algorithms."

Artificial intelligence is a much-discussed topic in medicine, especially in the field of diagnostics. "We aimed to investigate the potential on the basis of a specific example," explains Prof. Joachim Schultze, a research group leader at the DZNE and head of the Department for Genomics and Immunoregulation at the LIMES Institute of the University of Bonn. "Because this requires large amounts of data, we evaluated data on the gene activity of blood cells. Numerous studies have been carried out on this topic and the results are available through databases. Thus, there is an enormous data pool. We have collected virtually everything that is currently available."

Artificial Intelligence can help detect one of the most common forms of blood cancer - acute myeloid leukaemia (AML) - with high reliability, new research has found. Their approach, based on the analysis of the gene activity of cells found in the blood, could support conventional diagnostics and possibly accelerate the beginning of therapy, said the study published in the journal iScience. In the early stages the symptoms of AML can resemble those of a bad cold. However, AML is a life-threatening disease that should be treated as quickly as possible. "With a blood test, as it seems possible on the basis of our study, it is conceivable that the family doctor would already clarify a suspicion of AML," said Joachim Schultze, a research group leader at the German Center for Neurodegenerative Diseases (DZNE).