Evidence map›Paper›PMID 39896621›Full record

ArticlebioRxiv : the preprint server for biology2025

Evolutionary Reasoning Does Not Arise in Standard Usage of Protein Language Models.

Yasha Ektefaie, Andrew Shen, Lavik Jain, Maha Farhat, Marinka Zitnik

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Yasha EktefaieEric and Wendy Schmidt Center, Broad Institute of Harvard and MIT, Cambridge, MA 02142.ORCID 0000-0003-2759-4470
Andrew ShenDepartment of Biomedical Data Science, Stanford University, Stanford, CA 94305.ORCID 0009-0005-1984-0653
Lavik JainDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA 02115.
Maha FarhatDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA 02115.ORCID 0000-0002-3871-5760
Marinka ZitnikDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA 02115.ORCID 0000-0001-8530-7228

Funding

Training Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8M
Measuring Neonatal RegionalizationR01HD108794 · NICHD · STANFORD UNIVERSITY · PI Jochen Profit, JEANNETTE A ROGOWSKI · 2023 to 2026
$2.8M
NHGRI NIH HHS T32 HG002295NICHD NIH HHS R01 HD108794
6 · The paper itself

Abstract

Protein language models (PLMs) are often assumed to capture evolutionary information by training on large protein sequence datasets. Yet it remains unclear whether PLMs can reason about evolution-that is, infer evolutionary relationships between sequences. We test this capability by evaluating whether standard PLM usage, frozen or fine-tuned embeddings with distance-based comparison, supports evolutionary reasoning. Existing PLMs consistently fail to recover phylogenetic structure, despite strong performance on sequence-level tasks such as masked-token and contact prediction. We present Phyla, a hybrid state-space and transformer model that jointly processes multiple sequences and is trained using a tree-based objective across 3,000 phylogenies spanning diverse protein families. Phyla outperforms the next-best PLM by 9% on tree reconstruction and 23% on taxonomic clustering while remaining alignment- and guide-tree-free. Although classical alignment pipelines achieve higher absolute accuracy, Phyla narrows the gap and achieves markedly lower end-to-end runtime. Applied to real data, Phyla reconstructs biologically accurate clades in the tree of life and resolves genome-scale relationships among

Identifiers

PMID39896621
PMCPMC11785049

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.