Top 1% Most Discussed Preprints
54 papers in the Αlpha¹ curation
April 2026
7 selected from ~4,000 preprintsScalable genotyping in fixed transcriptomes resolves clonal heterogeneity via single-cell sequencing
Blattman, S. B.; Maslah, N.; Varela, A. A.; Kumpaitis, K.; Nalbant, B.; Snopkowski, C.; Mariani, M.; Kida, L. C.; Takizawa, M.; Ratnayeke, N.; Yu, K. K. H.; Fernandes, S.; Mousavi, N.; Borgstrom, E.; Vallejo, D.; Boghospor, L.; Xin, R.; Mignardi, M.; Wu, S.; Scarlott, N.; Delgado-Rivera, L.; Kumar, P.; Krishnan, S.; Giraudier, S.; Kiladjian, J.-J.; Howitt, B. E.; Kohlway, A.; Lund, P.; Pe'er, D.; Chaligne, R.; Lareau, C. A.
GIFT genotypes hundreds of mutations while reading the full transcriptome from fixed single cells. It's like giving old FFPE samples a high-tech DNA barcode upgrade, revealing how mutant clones drive inflammation in blood cancers.
An imaging flow cytometry method to study platelet-monocyte aggregates using Long COVID as a model
Thompon, A.; Venter, C.; de Villiers, W. J.; De Swardt, D.; Laubscher, G. J.; Kell, D. B.; Pretorius, E.
A new high-res flow cytometry method detects sticky platelet-monocyte clumps that fuel clotting and inflammation in Long COVID. Broadly applicable to any post-viral thrombo-inflammatory condition.
Functional characterization of bat limb regulatory elements
Ushiki, A.; Kelman, G.; Sheng, R.; Murray, E.; Eckalbar, W.; Zhang, Y.; Nobuhara, M.; Rajani, R.; Friess, K.; Barskyi, V.; Ngo, K.; Kinoshita, S.; Schlebusch, S. A.; Mason, M.; Zhan, S.; Liang, M.; Fong, S.; Haider, M. Y.; Singhal, V.; Schountz, T.; Hockman, D.; Illing, N.; Kaplan, T.; Ahituv, N.
Enhancers and gene expression tweaks explain how tiny rodent limbs morph into bat wings. A developmental genetics crossover highlighting evolution's tinkering at the DNA level.
Intranasal Anti-CD3 Antibody Treatment Attenuates Post-COVID Neuroinflammation and Enhances Hippocampal Neurogenesis and Cognitive Function in Mice
Lu, P.; Izzy, S.; Da Silva, P.; Imkamp, H. T.; Christenson, J. R.; Yahya, T.; Mansi, M. H. A.; Alawi, A.; Moreira, T. G.; Monje, M.; Weiner, H. L.; Iwasaki, A.
In a mouse model of Long COVID brain fog, a nasal squirt of anti-CD3 antibody acts like an immune reset button—even weeks after infection. It dampens cranky microglia, boosts neuron birth in the hippocampus, and sharpens memory.
Force transmission balance through adhesions determines multicellular handedness
Ishibashi, T.; Nishizawa, R.; Ogita, G.; Tokushige, N.; Shibata, T.
Cells decide their collective "lefty or righty" through a tug-of-war of forces at adhesions. Cell-cell and cell-substrate pulls together determine which way the whole tissue twists.
EGP1K: Whole-Genome Sequencing of 1,024 Egyptians Characterizes Population Structure and Genetic Diversity
Amer, K.; Moustafa, A.; Hassan, W. A.; Adel, E.; AbdElaal, K. R.; Ghanim, T. A.; Abd El-Raouf, A.; El-Hosseiny, A.; El-Sayed, A. F.; Badr, A. H.; Hassan, A.; Kotb, A.; Ragheb, A.; Muhammad, A. M.; Ali, A.; Abdelaal, A.; Ramadan, E.; El-Garhy, F. M.; El Shehaby, H.; Ali, M. A.; Albarbary, M.; Zahra, M. A.; Amer, M.; Elmonem, M. A.; Fahmy, N. T.; Abdel-Haseeb, O. M.; Hassan, T. M.; Daoud, Y. A.; Howeedy, Y.; Farouk, Y. K.; Soror, S.; El-Feky, G.; Sakr, M.; Soliman, N. A.; Gad, Y. Z.; Abdel-Ghaffar, K. A.; Egypt Genome Consortium,
Sequencing over a thousand Egyptian genomes reveals the rich genetic tapestry of the region, painting a detailed picture of population structure and diversity that fills a major gap in North African genomics—like finally zooming in on a long-blurry part of the human family portrait.
A Rapid and Universal Pipeline for High-Resolution GPCR Structure Determination through In Silico Construct Optimization and de novo Protein Design
Kojima, A.; Kawakami, K.; Kobayashi, N.; Kobayashi, K.; Matsui, T. E.; Uemoto, K.; Gu, Y.; Narita, T. J.; Kugawa, M.; Fukuda, M.; Kato, H. E.
GPCR structures used to be a nightmare of linker tweaks, but this pipeline uses in silico optimization and de novo design to crank out high-res antagonist-bound structures like a universal 3D-printing factory for tricky membrane proteins.
March 2026
16 selected from ~4,000 preprintsTransient contractility attenuation reprograms epithelial cells into a protrusion-driven state that drives tissue fluidization
WP, S.; Liu, S.; Nguyen, T. P.; Mishra, P. K.; Pratiman, D.; Gupta, A. S.; Hirashima, T.
Jammed epithelial cells get a quirky blebbistatin chill pill on their contractility, flipping them into protrusion-happy movers that fluidize the tissue like a molecular rave turning stiff crowds into flowing, ERK-rewired party animals with boosted traction.
Tabula Sapiens reveals the non-coding RNA landscape across 22 human organs and tissues
Lee, J.; Mantri, M.; Murthy, K.; Seeker, L. A.; Crowley, G.; Jones, R. C.; Tabula Sapiens Consortium, ; Quake, S. R.
The Tabula Sapiens sequel goes rogue on non-coding RNAs via total RNA-seq, exposing cell-type-specific tRNA drama, nuclear-cytoplasmic hide-and-seek, and senescence plot twists that make protein-coding genes look like the boring straight men in the transcriptome comedy.
Cross-species single-cell atlases chart progression, therapy-driven remodelling and immune evasion in pancreatic cancer
Lucarelli, D.; Parikh, S.; Jimenez, S.; Schneeweis, C.; Ngandiri, D. A.; Putze, P.; Kos, T.; Wellappili, D.; Goelling, V.; Kuerbanjiang, M.; Shull, C.; Litwinski, M. R.; Handschuh, T. B.; Dabiri, Y.; Zukowska, M.; Seidler, B.; Kfuri-Rubens, R.; Baerthel, S.; Halle, L.; Arbesfeld-Qiu, J. M.; Gong, D.; Schneider, G.; Rad, R.; Falcomata, C.; Schmidt-Supprian, M.; Hwang, W. L.; Theis, F. J.; Saur, D.
In a massive 1.6-million-cell nanoscale PDAC spy novel, human and mouse tumors swap notes on progression and radiotherapy's sneaky EMT-persistent villainy, with orthotopic models hilariously stealing the show as the most faithful mimics while rare double-positive T cells crash the immune party.
X-Cell: Scaling Causal Perturbation Prediction Across Diverse Cellular Contexts via Diffusion Language Models
Wang, C.; Karimzadeh, M.; Ravindra, N. G.; Bounds, L. R.; Alerasool, N.; Huang, A. C.; Ma, S.; Gulbranson, D. R.; Cui, H.; Lee, Y.; Arjavalingam, A.; MacKrell, E. J.; Wilken, M. S.; Chen, J.; Herken, B. W.; Weber, J. A.; Onesto, M. M.; Gonzalez-Teran, B.; Leung, N. F.; Shi, S. Y.; Smith, B. J.; Lam, S. K.; Barner, A.; Wright, P.; Rumsey, E. M.; Kim, S.; Sit, R. V.; Litterman, A. J.; Chu, C.; Wang, B.
Xaira’s massive 4.9B-parameter “virtual cell” acts like a diffusion-language fortune teller, zero-shot predicting gene expression chaos from CRISPR hits across unseen cell types using a whopping 25M+ perturbed transcriptomes in pure LLM power-law style.
Behavioral, Physiological, and Transcriptional Mechanisms of Memory in a Synthetic Living Construct
Pai, V. P.; Traer, J. A.; Sperry, M. M.; Zeng, Y.; Levin, M.
Imagine a blob of frog skin with no brain that can still "remember" things. These "xenobots" use weird calcium waves to store memories of chemical hits for days. It’s basically a biological hard drive made of lab-grown slime—proving you don't actually need a brain to have a memory.
Genome-scale functional mapping of the mammalian whole brain with in vivo Perturb-seq
Shi, T.; Korshunova, M.; Kim, S.; DeTomaso, D.; Zheng, X.; Vishvanath, L.; Nyasulu, T.; Huynh, N.; Sun, A.; Thompson, P. C.; Zhang, Y.; Wigdor, E. M.; Rohani, N.; Ali, S.; Qiu, H.; Geralt, M.; Zhao, Z.; Rabhi, S.; Yao, Z.; van Velthoven, C. T.; Nery, J. R.; Castanon, R. G.; Dicks, S.; Chen, T. J.; Ecker, J. R.; Zeng, H.; Zheng, G. X.; Sanders, S. J.; Sundaram, L.; Jin, X.
A 7.7-million-cell brain heist where 1,947 disease genes get CRISPR-mugged in living mice, revealing cell-type-specific plot twists—like NMDA subunits throwing opposing transcriptional tantrums—while turning the whole mouse brain into a living "virtual cell" atlas for neuro quirks.
TRAILBLAZER: generative multicellular perturbation model of biology
Nener, J.; Selvamani, P.; Badarinarayan, S. S.; Chandramohan, N.; Grzybowski, A. T.
TRAILBLAZER is a transformer that models entire multicellular neighborhoods at once, predicting how patient cell populations will react to drugs in zero-shot—think a hyperspherical crystal ball that ranks immunomodulators like a quirky matchmaker for your immune system.
OmicClaw: executable and reproducible natural-language multi-omics analysis over the unified OmicVerse ecosystem.
Zeng, Z.; Wang, X.; Luo, Z.; Zheng, Y.; Hu, L.; Xing, C.; Du, H.
Forget wrestling with code—OmicClaw lets you boss around massive multi-omics datasets using plain English, turning your wildest analysis dreams into traceable, reproducible workflows that even AI agents can execute without going rogue.
Selection-free whole genome transplantation revives dead microbes
Seidel, Z. P.; Assad-Garcia, N.; Paralanov, V.; Wu, F.; Chao, O.; Strychalski, E. A.; Romantseva, E. F.; Goshia, T.; Venter, J. C.; Glass, J. I.
In a zombie-synth-bio heist straight out of a mad-scientist flick, the Venter crew chemically “kills” Mycoplasma cells with Mitomycin C crosslinks, then stuffs their empty shells with synthetic genomes via whole-genome transplantation—reviving them as fully functional synthetic bacteria with zero selection-marker drama, like the ultimate microbial resurrection hack.
Persistent SARS-CoV-2 Spike is Associated with Localized Immune Dysregulation in Long COVID Gut Biopsies
Abraham Soria, S.; Peterson, P.; VanElzakker, M. B.; Tankelevich, M.; Mehandru, S.; Proal, A.; Putrino, D.; Freire, M.
Long COVID's pesky SARS-CoV-2 Spike protein crashes the gut party, cranking up Crohn’s-esque genes and muting immune traffic cops in a bizarre pro-inflammatory tango, turning the colon into a dysfunctional disco where the virus refuses to leave the dance floor.
Genome delivery of a contractile tailed phage and its superinfection exclusion mechanism
Roa-Eguiara, A.; Marin-Arraiza, L.; Klein-Sousa, V.; Santiveri, M.; Rutbeek, N. R.; Piel, D.; Pape, T.; Sofos, N.; Hendriks, I. A.; Nielsen, M. L.; Hu, H.; Harms, A.; Taylor, N. M. I.
In a nanoscale espionage saga, bacteriophage T4 deploys its genome into E. coli with a tape measure protein pulling the strings like a quirky puppet master, while the Imm protein acts as a viral bouncer, hilariously slamming the door on unwanted phage crashers.
An Energy Landscape Approach to Miniaturizing Enzymes using Protein Language Model Embeddings
Lala, J.; Agrawal, H.; Dong, F.; Wells, J.; Angioletti-Uberti, S.
This AI tool acts like a shrink ray for proteins. It takes bulky, complex enzymes and designs "Mini-Me" versions that are tiny but still work perfectly. These pocket-sized enzymes are way easier to handle in the lab and are now available for anyone to download and test.
Single-Cell Genomics Decontamination with CellSweep
Caskey, M.; Rich, J.; Weber, R.; Mortazavi, A.; Pachter, L.; Hallgrimsdottir, I. B.
Single-cell data is usually full of "background noise"—like trying to hear a conversation in a loud stadium. CellSweep acts like a high-powered vacuum cleaner, sucking up all the digital gunk and ambient "ghost" RNA so that scientists can actually see what the cells are doing.
RNA-seq analysis in seconds using GPUs
Melsted, P.; Guthnyjarson, E. M.; Nordal, J.
Bioinformatics just got a nitro boost. An Icelandic team rebuilt the industry-standard software to run on high-powered GPUs. Now, a massive data crunch that used to take a 40-minute lunch break is finished in 50 seconds. It’s "blink-and-it’s-done" wizardry for genomic data.
Learning functional groups in complex microbiomes
Schmitt, M. S.; Lee, K.; Bunbury, F.; Landsittel, J. A.; Vitelli, V.; Kuehn, S.
From soil to the gut, communities composed of thousands of microbes perform functions such as carbon sequestration and immune system regulation. Here, we introduce a data-driven approach that explains…
Towards building a World Model to simulate perturbation-induced cellular dynamics by AlphaCell
Chuai, G.; Chen, X.; Yang, X.; Zhang, C.; Qu, K.; Wang, Y.; Li, W.; Yang, J.; Si, D.; Xing, F.; Gao, Y.; Wu, S.; Fu, S.; He, B.; Liu, Q.
Think of this as "The Sims" but for real biology. AlphaCell treats the inside of a cell like a video game physics engine. It can predict exactly how a cell will freak out when you hit it with a drug or a mutation—allowing scientists to run experiments in a digital world without ever touching a pipette.
February 2026
10 selected from ~4,000 preprintsMicrobiota-derived extracellular vesicles link intestinal dysbiosis to neuroimmune activation in long COVID
Aranguren, M.; Doyon-Laliberte, K.; Boncheva, I.; Villard, A.; Desjardins, A.; Darbinian, E.; Patel, S.; DuSablon, C.; Rivera Conde, E.; Cabrera Munoz, D.; Purchase, L.; Piscopo, V. E. C.; Alluli, A.; Benaliouad, F.; Sirois, J.; Durcan, T.; Masse, C.; Mlaga, K. D.; Chandrasekaran, P.; Poudrier, J.; Falcone, E. L.
Post COVID-19 condition (Long COVID, LC) is frequently accompanied by persistent neurological symptoms, but the mechanisms linking intestinal dysbiosis to neuroinflammation remain unclear. Here we ide…
In vivo lineage tracing across human tissues using methylation barcodes in the protocadherin gene cluster
Hackett, S. F.; Boniface, C. T.; Fonseca, A. V. A.; Ramos-Yamasaki, A. D.; Watson, C.; Bazin, H. M. L.; Tan, A. B.; Lee Yu, H.; Hanssen, L. L. P.; Dev, H.; Apostolidou, S.; Gentry-Maharaj, A.; Esener, S.; Menon, U.; Blundell, J. R.
Hijacking the brain's quirky protocadherin methylation for a full-body barcode bash, this method tracks clonal expansions like a sneaky cellular detective, spotting hidden growths in blood and organs that traditional mutation sleuths miss with epimutation flair.
The Virtual Biotech: A Multi-Agent AI Framework for Therapeutic Discovery and Development
Zhang, H. G.; Eckmann, P.; Miao, J.; Mahon, A. B.; Zou, J.
Picture a squad of AI agents cosplaying as a biotech startup, zipping through mountains of clinical trials and genomics data like overcaffeinated interns, uncovering that cell-specific targets make drugs 40-48% more successful while dodging side effects with sassy precision.
A Cross-Species Enhancer-AAV Toolkit for Cell Type-Specific Targeting Across the Basal Ganglia
Wirthlin, M. E.; Hunker, A. C.; Somasundaram, S.; Lerma, M. N.; Laird, W. D.; Omstead, V.; Taskin, N.; Kempynck, N.; Schmitz, M. T.; Gao, Y.; Thomas, E.; Hooper, M.; Ben-Simon, Y.; Martinez, R. A.; Opitz-Araya, X.; Mich, J. K.; Oster, A.; Dwivedi, D.; Groce, E.; Roth, J.; Thyagarajan, B.; Way, S.; Amaya, A.; Ayala, A.; Barta, S.; Bertagnolli, D.; Bixby, M.; Cardenas, T.; Casper, T.; Clark, M.; Donadio, N.; Dotson, N. I.; Egdorf, T.; Peterson, E. L.; Gloe, J.; Goldy, J.; Grasso, C.; Han, W.; Hastings, S. D.; Hewitt, M.; Hirschstein, D.; Ho, W.; Huang, A.; Johnson, T.; Jones, D.; Jordan, A.; Jun
The mammalian basal ganglia (BG) orchestrate motor, cognitive, and affective functions, yet cell type-specific genetic access remains limited, especially beyond rodents. Key structures implicated in m…
Differential analysis of genomics count data with edge*
Pachter, L.
Lior Pachter, with a sprinkle of AI wizardry from Claude and Codex, teleports the venerable edgeR from R to Python in a mere week, birthing edgePython that jazzes up single-cell analysis with Empirical Bayes flair, leaving bioinformatic glitches in the dust.
Systematic reviews in minutes to hours using artificial intelligence
Bakker, L.; Caganek, T.; Rooprai, A.; Hume, S.
Systematic reviews are used in academia, biotechnology, pharmaceutical companies and government to synthesise and appraise large numbers of publications. The current (largely manual) workflow takes an…
Xiao, W.; Zhang, Y.; Gong, C.; Zhang, H.; Ma, W.; Liu, Z.; Chen, X.; Guan, J.; Wang, L.
We introduce Protenix-v1 (PX-v1), the first open-source structure prediction model to attain superior performance to AlphaFold3 while strictly adhering to the same training data cutoff, model size, an…
Using a GPT-5-driven autonomous lab to optimize the cost and titer of cell-free protein synthesis
Smith, A. A.; Wong, E. L.; Donovan, R. C.; Chapman, B. A.; Harry, R.; Tirandazi, P.; Kanigowska, P.; Gendreau, E. A.; Dahl, R. H.; Jastrzebski, M.; Cortez, J. E.; Bremner, C. J.; Hemuda, J. C. M.; Dooner, J.; Graves, I.; Karandikar, R.; Lionetti, C.; Christopher, K.; Consiglio, A. L.; Tran, A.; McCusker, W.; Nguyen, D. X.; Nunes da Silva, I. B.; Bautista-Ayala, A. R.; McNerney, M. P.; Atkins, S.; McDuffie, M.; Serber, W.; Barber, B. P.; Thanongsinh, T.; Nesson, A.; Lama, B.; Nichols, B.; LaFrance, C.; Nyima, T.; Byrn, A.; Thornhill, R.; Cai, B.; Ayala-Valdez, L.; Wong, A.; Che, A. J.; Thavaraj
We used an autonomous lab, comprising a large language model (LLM) and a fully automated cloud laboratory, to optimize the cost efficiency of cell-free protein synthesis (CFPS). By conducting iterativ…
Virtual Cells Need Context, Not Just Scale
Dibaeinia, P.; Babu, S.; Knudson, M.; ElSheikh, A.; Wen, Y.; Liu, H.; Perera, J.; Khan, A. A.
The intersection of AI and biology has entered a phase of explosive growth, driven by the ambition to build "Virtual Cells" or computational models capable of predicting cellular responses to any pert…
Critical assessment of intratumor and low-biomass microbiome using long-read sequencing
Zhang, Y.; Mead, E. A.; Ni, M.; Ksiezarek, M.; Liu, Y.; Cao, L.; Chen, H.; Fan, Y.; Qiao, W.; Li, Y.; Zuluaga, L.; Deikus, G.; Sebra, R.; Brody, R.; Yong, R. L.; Badani, K. K.; Zhang, X.-S.; Fang, G.
The detection of low-biomass microbial DNA in human tissues is often confounded by contamination, as demonstrated in the debates over the existence of microbiomes in the placenta, brain, blood, and tu…
January 2026
9 selected from ~4,000 preprintsDecoding the MYC locus reveals a druggable ultraconserved RNA element
Shi, P.; Yang, F.; FNU, T.; Huang, W.; Aparicio, A. O.; Kalicki, C. H.; Trehan, A.; Murphy, M. R.; Rotlevi, E. R.; Xing, L.; Reilly, M. P.; Que, J.; Wu, X.
The human genome is dominated by noncoding sequences, most of which are poorly conserved across species. How genetic information is distributed between coding and noncoding regions remains a fundament…
A Single-Cell and Spatial 3D Multi-omic Atlas of Developing Human Basal Ganglia and Inhibitory Neurons
Heffel, M. G.; Xu, H.; Pastor-Alonso, O.; Li, X.; Baig, M. S.; Irfan Ghoor, R.; Li, R.; Kern, C.; Kum, J.; Zhang, Y.; Paino, J.; Tsai, M. J.; Tai, C.-Y.; Tucker, G.; Zhao, Z.; Hou, A.; von Behren, Z.; Bhade, M.; Li, S.; Sandoval, K.; Scholes, J.; Codrea, F.; Calimlim, J.; Liao, E. K.; Leung, G.; Kim, J.; Eskin, E.; Flint, J.; Cotter, J. A.; Pasaniuc, B.; Bintu, B.; Zhu, Q.; Mukamel, E. A.; Ernst, J.; Paredes, M. F.; Luo, C.
The human basal ganglia (BG), subcortical nuclei fundamental to motor regulation and cognitive modulation, is constructed from neurons produced during gestation in the adjacent ganglionic eminences (G…
The Demographic and GDP Impacts of Slowing Biological Aging
Romanni-Klein, R.; Hendrix, N.; DeBacker, J.; Evans, R.
Biological aging imposes significant socio-economic costs, increasing health expenses, reducing productivity, stalling population growth and straining social systems, culminating in reduced economic a…
cyto: ultra high-throughput processing of 10x-flex single cell sequencing
Teyssier, N.; Dobin, A.
Single-cell genomics is rapidly scaling toward billion-cell atlases, but computational analysis has become a critical bottleneck. Processing multiplexed datasets with existing tools requires substanti…
vir2vec: A Genome-Wide Viral Embedding
Rancati, S.; Arozarena Donelli, P.; Nicora, G.; Bergomi, L.; Buonocore, T.; Sy, M. A.; Pandey, S.; Prosperi, M.; Salemi, M.; Bellazzi, R.; Boucher, C.; Parimbelli, E.; Marini, S.
Genomic language models (gLMs) have recently emerged as powerful numerical surrogates for DNA, but existing architectures are largely focused on human DNA or trained on limited viral references, and n…
The microtubule GTP-tubulin cap size is modulated during cell division
Cassidy, A. C.; Burnette, D. T.; Zanic, M.
Microtubule dynamics change during cell division to enable rapid microtubule network remodeling. The switching from microtubule growth to shrinkage is attributed to the loss of a stabilizing GTP-cap s…
De novo protein ligand design including protein flexibility and conformational adaptation
Agamia, J.; Zacharias, M.
MotivationThe rational design of chemical compounds that bind to a desired protein target molecule is a major goal of drug discovery. Most current molecular docking but also fragment-based build-up or…
Fendioxypyracil, a new and systemic PPO-inhibiting herbicide for X-spectrum weed control
Seiser, T.; Porri, A.; Johnen, P.; Zeyer, S.; Wahrheit, J.; Betz, M.; Vandenberghe, B.; Asher, S.; Parra, L.
BackgroundFendioxypyracil is a novel protoporphyrinogen oxidase (PPO)-inhibiting herbicide (HRAC Group 14) developed to address the increasing prevalence of herbicide-resistant weeds and to expand ava…
Benchmarking algorithms for RNA velocity inference
Huang, K.; Zhou, Y.; Wang, T.; Li, X.; Zhao, X.; Liu, X.; Huang, L.; Zhou, X.; Liu, J.
RNA velocity is a computational framework for single-cell RNA sequencing (scRNA-seq) that estimates the future transcriptional state of individual cells, thereby capturing the direction and rate of ce…
December 2025
6 selected from ~4,000 preprintsPeptiVerse: A Unified Platform for Therapeutic Peptide Property Prediction
Zhang, Y.; Tang, S.; Chen, T.; Mahood, E.; Vincoff, S.; Chatterjee, P.
Therapeutic peptides combine the advantages of small molecules and antibodies, offering target flexibility and low immunogenicity, yet their successful translation requires careful evaluation of multi…
Jang, Y.; Qin, Q.-Q.; Wang, J.-L.; Kornmann, B.
Remarkable progress has been achieved by machine learning, particularly in accurate prediction of protein tertiary structures. Despite these advances, accurately annotating protein functions through m…
Prediction of transformative breakthroughs in biomedical research
Davis, M. T.; Busse, B. L.; Arabi, S.; Meyer, P.; Hoppe, T. A.; Meseroll, R. A.; Hutchins, B. I.; Willis, K. A.; Santangelo, G. M.
The ability to predict scientific breakthroughs at scale would accelerate the pace of discovery and improve the efficiency of research investments. Recent advances in artificial intelligence, graph th…
Mapping Gene Impact on Single-cell Transcriptomic Networks via Perturbation Response Scanning
Gupta, S.; Romero, S.; Cai, J. J.
Gene knockout experiments are essential for dissecting gene function, and CRISPR has made targeted gene disruption more accessible than ever. Single-cell CRISPR screening enables the construction of r…
Kalfon, J.; Peyre, G.; Cantini, L.
Cell biology has been booming with foundation models trained on large single-cell RNA-seq databases, but benchmarks and capabilities remain unclear. We propose an additive benchmark across a gymnasium…
A secreted endosymbiont protein essential for colonizing host cells
Maeda, G. P.; Xue, A. Z.; Smith, T. E.; Sundar, A.; Powell, J. E.; Yu, E. W.; Moran, N. A.
ABSTRACTIntracellular bacterial symbioses have arisen myriad times in eukaryotes, with dozens known from insects alone1,2. Beginning with Buchnera, the obligate endosymbiont of aphids, genomes of endo…
November 2025
6 selected from ~4,000 preprintsSpatialProp: tissue perturbation modeling with spatially resolved single-cell transcriptomics
Sun, E. D.; Buendia, A.; Brunet, A.; Zou, J.
Perturbational studies are the gold standard for identifying causal relationships between components of biological systems. Recent technological advances, including Perturb-seq and related assays, hav…
LoL-align: sensitive and fast probabilistic protein structure alignment
Reifenrath, L.; van Kempen, M.; Kim, G.; Kim, S. H.; Radnezhad, M.; Mirdita, M.; Steinegger, M.; Söding, J.
The ubiquitous availability of protein structures permits replacing sequence alignment with more accurate and sensitive structure alignment algorithms. LoL-align maximizes a local log-odds score for p…
Evo2HiC: a multimodal foundation model for integrative analysis of genome sequence and architecture
Fang, T.; Wang, X.; Xiao, Z.; Hang, S.; Murtaza, G.; Yang, J.; Xu, H.; Jha, A.; Noble, W. S.; Wang, S.
Understanding how genomic sequences shape three-dimensional (3D) genome architecture is funda-mental to interpreting diverse biological processes. Although previous studies have shown that sequence in…
Lanna, A.; Valvo, S.; Dustin, M.; Rinaldi, F.
The role of the immune system in regulating organismal lifespan remains poorly understood. Here, we show that CD4 T cells release "telomere Rivers" into circulation after acquiring telomeres from anti…
Atacformer: A transformer-based foundation model for analysis and interpretation of ATAC-seq data
LeRoy, N. J.; Zheng, G.; Khoroshevskyi, O.; Campbell, D. R.; Zhang, A.; Sheffield, N. C.
IntroductionChromatin accessibility profiling is an important tool for understanding gene regulation and cellular function. While public repositories house nearly 10,000 scATAC-seq experiments, unifyi…
MERFISH+, a large-scale, multi-omics spatial technology resolves the molecular holograms of the 3D human developing heart
Kern, C.; Zhang, Q.; Lu, Y.; Eschbach, J.; Zeng, Z.; Farah, E. N.; Tai, C.-Y.; Yang, K.; Jenie, I.; Yao, F.; Zhao, Z.; Ma, Q.; Padilla, C. G.; Monell, A.; Moghadami, S.; Zhu, F.; Li, B.; Hou, A.; Tucker, G.; Ellison, D.; Chi, N. C.; Qiu, X.; Zhu, Q.; Bintu, B.
Hybridization-based spatial transcriptomics technologies have advanced our ability to map cellular and subcellular organization in complex tissues. However, existing methods remain constrained in gene…