arXiv subjects

Aris Karatzikos

Publications and source records attributed to Aris Karatzikos.

3 recordsLinked to original sources

arXiv2026

Artificial intelligence and biosecurity: capabilities, threat pathways, and defense-in-depth governance

Artificial intelligence is reshaping biological research across an increasingly connected digital-to-physical workflow. General-purpose large language models can retrieve and integrate scientific information, support experimental planning, and computational analysis; biological foundation models can predict, optimize, and generate proteins, genes, and genome-scale sequences; agentic systems can coordinate multistep research tasks; automated laboratories can partially close the design-build-test-learn cycle. These technologies could greatly benefit medicine, public health, and biotechnology. However, their biosecurity risk depends not only on what the AI can do, but also on who uses it, their expertise and intent, their access to laboratory tools and materials, and the safeguards in place. Current evidence shows that AI uplift exists but primarily affects digital rather than physical tasks. Frontier systems have exceeded expert baselines on in-silico, and screening-evasion benchmarks, whereas controlled wet-laboratory studies find that tacit knowledge and physical execution remain substantial barriers. This review describes the different biological threats from AI tool use, from information gathering and biological design to procurement, synthesis, testing, scale-up, and potential release. We further examine why alignment techniques for general-purpose models transfer poorly to biological ones, and the emerging role of interpretability in auditing whether hazardous capabilities are genuinely removed. We argue for defense-in-depth governance that links capability thresholds to proportionate responsibilities across the biological AI ecosystem, reducing high-consequence risk while preserving beneficial use.

cs.AI↗

arXiv2026

Structure is not mechanism: high-gain gated-FFN rows across text and genomic foundation models

A small number of unusually high-gain parameters can exert disproportionate effects in transformer language models, but whether analogous structures recur in genomic foundation models and whether structural geometry determines functional importance remains unknown. We analyzed high-gain rows in gated feed-forward networks across text and genomic foundation models, including a frozen 22-model causal census. Computing an associated bilinear weight operator exactly, without a diagonal approximation, we tested whether structural extremeness is a transferable mechanism. Activation-derived candidates were functionally enriched relative to random and top-norm same-layer controls, yet neither spectral concentration nor operator magnitude predicted causal effect size, and these associations vanished within the endpoint-homogeneous text-decoder subset. A within-layer sweep of 36 rows in one genomic and one text decoder resolved this into two regimes: below the detector's acceptance threshold the ratio carried no positive information about causal damage, whereas above it the ratio ordered rows strongly but did not grade severity as a dose-response. The same sweep revealed a second individually catastrophic row invisible to a one-candidate-per-model census, and non-additive damage among co-located critical rows. Case studies showed divergent causal organizations: a robust super-additive pair interaction in DNABERT-2, and in GENERator a sharply position-localized dependence in which preserving or restoring the row's beginning-of-sequence contribution rescued essentially all native-loss damage. High-gain gated-FFN rows are therefore a recurrent architectural phenotype whose structural prominence acts as an enrichment signal, not a calibrated measure of functional criticality or a specification of causal organization. Enrichment is general, but the mechanism is model-specific.

q-bio.GN↗

arXiv2025

Investigating DNA words and their distributions across the tree of life

The frequency distributions of DNA k-mers are shaped by fundamental biological processes and offer a window into genome structure and evolution. Inspired by analogies to natural language, prior studies have attempted to model genomic k-mer usage using Zipf's law, a rank-frequency law originally formulated for words in human language. However, the extent to which this law accurately captures the distribution of k-mers across diverse species remains unclear. Here, we systematically analyze k-mer frequency spectra across more than 225,000 genome assemblies spanning all three domains of life and viruses. We demonstrate that Zipf's law consistently underperforms in modeling k-mer distributions. In contrast, we propose the truncated power law and Zipf-Mandelbrot distributions, which provide substantially improved fits across taxonomic groups. We show that genome size and GC content influence model performance, with larger and GC-content imbalanced genomes yielding better adherence. Additionally, we perform an extensive analysis on vocabulary expansion and exhaustion across the same organisms using Heaps' law. We apply our modeling framework to evaluate simulated genomes generated by k-let preserving shuffling and deep generative language models. Our results reveal substantial differences between organismal genomes and their synthetic or shuffled counterparts, offering a novel approach to benchmark the biological plausibility of artificial genomes. Collectively, this work establishes new standards for modeling genomic k-mer distributions and provides insights relevant to synthetic biology, and evolutionary sequence analysis.

q-bio.GN↗