SUMMARY The common approach to the multiplicity problem calls for controlling the familywise error rate (FWER). This approach, though, has faults, and we point out a few. A different approach to problems of multiple significance testing is presented. It calls for controlling the expected proportion of falsely rejected hypotheses — the false discovery rate. This error rate is equivalent to the FWER when all hypotheses are true but is smaller otherwise. Therefore, in problems where the control of the false discovery rate rather than that of the FWER is desired, there is potential for a gain in power. A simple sequential Bonferronitype procedure is proved to control the false discovery rate for independent test statistics, and a simulation study shows that the gain in power is substantial. The use of the new procedure and the appropriateness of the criterion are illustrated with examples.
The control of the false discovery rate in multiple testing under dependency
Benjamini and Hochberg suggest that the false discovery rate may be the appropriate error rate to control in many applied multiple testing problems. A simple procedure was given there as an FDR controlling procedure for independent test statistics and was shown to be much more powerful than comparable procedures which control the traditional familywise error rate. We prove that this same procedure also controls the false discovery rate when the test statistics have positive regression dependency on each of the test statistics corresponding to the true null hypotheses. This condition for positive dependency is general enough to cover many problems of practical interest, including the comparisons of many treatments with a single control, multivariate normal test statistics with positive correlation matrix and multivariate $t$. Furthermore, the test statistics may be discrete, and the tested hypotheses composite without posing special difficulties. For all other forms of dependency, a simple conservative modification of the procedure controls the false discovery rate. Thus the range of problems for which a procedure with proven FDR control can be offered is greatly increased.
Assessing and mitigating batch effects in large-scale omics studies
Batch effects in omics data are notoriously common technical variations unrelated to study objectives, and may result in misleading outcomes if uncorrected, or hinder biomedical discovery if over-corrected. Assessing and mitigating batch effects is crucial for ensuring the reliability and reproducibility of omics data and minimizing the impact of technical variations on biological interpretation. In this review, we highlight the profound negative impact of batch effects and the urgent need to address this challenging problem in large-scale omics studies. We summarize potential sources of batch effects, current progress in evaluating and correcting them, and consortium efforts aiming to tackle them.
LLM-Assisted Reanalysis of Unsolved Rare Disease Genomes Increases Diagnostic Yield
Rare and undiagnosed genetic disorders affect millions of patients globally, and many patients endure years of inconclusive testing. Conventional genomic interpretation can be insufficiently sensit...
Accelerating scientific discovery with Co-Scientist
Scientific discovery is driven by scientists generating novel hypotheses for complex problems that undergo rigorous experimental validation. To augment this process, we introduce Co-Scientist, a multi-agent AI system built on Gemini for structured scientific thinking and hypothesis generation. Co-Scientist aims to help scientists discover new original knowledge. Conditioned on their research objectives and prior scientific evidence, it formulates demonstrably novel research hypotheses for experimental verification. The system's design involves agents continuously generating, critiquing and refining hypotheses accelerated by scaling test-time compute. Key contributions include: (1) a multi-agent architecture with an asynchronous task execution framework for flexible compute scaling; (2) a tournament evolution process for self-improving hypotheses generation. Automated evaluations show continued benefits of test-time compute scaling, improving hypothesis quality over time. While general purpose, we focus the validation in three biomedical applications: drug repurposing, novel target discovery, and explaining mechanisms of anti-microbial resistance. Specifically, Co-Scientist helped identify new drug repurposing candidates and synergistic combination therapies for acute myeloid leukemia, which were validated through in vitro experiments. These real-world validations demonstrate the potential of Co-Scientist to accelerate scientific discovery and usher in an era of AI empowered scientists.
Hypothesis: A new approach to property-based testing
The property-based testing library for Python
GraphDx: A Cost-Aware Knowledge-Enhanced Multi-Agent Framework for Sequential Diagnosis
Unlike static question answering, sequential diagnosis mirrors actual clinical workflows: physicians iteratively gather information through symptom inquiries and diagnostic tests, making decisions under uncertainty while balancing diagnostic accuracy against resource costs including monetary expense, patient discomfort, and time. This multi-turn process requires not merely knowledge recall, but systematic reasoning that coordinates information acquisition with hypothesis refinement.
A universal approach to mocking
Defunctionalise your continuations and your tests can run any computation a step at a time.
LLMs believe false statements even after explicit warnings that they're false
Fine-tuning tests show "bias... toward confidently representing the claims as true."
Why Most Published Research Findings Are False
Summary There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.
Multiple Hypothesis Testing
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The natural selection of bad science
Abstract. Poor research design and data analysis encourage false-positive findings. Such poor methods persist despite perennial calls for improvement, sugg
Scaling Discovery through Test-Time Communication
Science advances not in isolation but through collaboration, yet existing agentic systems capture little of this. Whether communicating agents help remains an open question with mixed prior results. We show that test-time communication can substantially outperform independent parallel attempts on challenging tasks, where sharing a breakthrough can push the whole group forward. We first study the effect of scaling multi-agent test-time communication, where agents have no predefined roles and communicate via a shared directory, on ARC-AGI-3, a benchmark requiring novel problem solving. We find that a team of $k$ communicating agents, team@$k$, matches the success rate of $4k$ independent agents, and this advantage grows with $k$, suggesting gains compound with scale. The effect is not merely efficiency: a task that no single agent can solve, a team of agents can solve reliably. Furthermore, these gains transfer to research-oriented tasks, given sufficient compute. On polyomino packing, communicating agents outperform best@$k$ and exceed the prior best-known score. On MNIST classifier compression, communication surpasses the best-known human solution. A team of four agents produced a 1,957-byte classifier submission achieving 99.4% test accuracy, smaller than both the best-known human solution and the best single-agent result. These gains are not unconditional. Independent agents may outperform communication when compute is limited or when a clear measure of progress is absent. However, under sufficient compute and clear feedback, multi-agent communication consistently yields stronger results.
Researchers published in NEJM about using OpenAI’s o3 DeepResearch to discover strong leads in 18 previously unsolved rare diseases o3 produced *explanations* of old lab results (not diagnoses), which researchers vetted and took to the lab AI is not just a black box openai.com/index/diagnose-rare-childhood…
Using AI to help physicians diagnose rare genetic diseases affecting children
openai.comOpenEvolve underperforms simple autmated discovery harnesses the rest are insignificant from each other. The best choice changed across model–problem pairs. We ran a controlled study (3m+ rollouts) using repeated budget-matched runs, strong baselines, and statistical hypothesis testing.
