Back

Phylogenetic tree inference using generative models

Dotan, E.; Schers, A.; Wygoda, E.; Pupko, T.; Belinkov, Y.

2026-06-16 bioinformatics
10.64898/2026.06.14.732140 bioRxiv
Show abstract

Accurate inference of phylogenetic trees is fundamental to evolutionary biology, yet existing methods rely on complex pipelines involving multiple sequence alignment, explicit evolutionary models, and computationally intensive tree search procedures. Here, we present BetaInfer, a generative framework that reformulates phylogenetic tree inference as a sequence transduction problem. BetaInfer leverages hybrid transformer-based architectures to directly map sets of unaligned sequences to phylogenetic trees represented in Newick format. Trained on large-scale simulated evolutionary data with known ground truth, BetaInfer learns to capture complex evolutionary signals directly from sequence data. Ensemble-based generation of multiple candidate trees further improves robustness, reducing reconstruction error by over 30% relative to single predictions. Across extensive evaluations on both simulated and empirical datasets, BetaInfer achieves competitive performance relative to state-of-the-art phylogenetic pipelines, matching, and in some cases exceeding, the accuracy of established likelihood-based and distance-based methods under a wide range of conditions. Interpretability analyses reveal that BetaInfer leverages internal pairwise-distance computations to synthesize evolutionary relationships into an integrated, global representation that supports direct tree generation. Together, these results demonstrate that generative models can serve as a viable and scalable alternative to standard phylogenetic pipelines.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

1
Systematic Biology
144 papers in training set
Top 0.1%
27.9%
2
Molecular Biology and Evolution
542 papers in training set
Top 0.8%
9.6%
3
Nature Communications
5641 papers in training set
Top 24%
6.6%
4
PLOS Computational Biology
1863 papers in training set
Top 8%
4.7%
5
Nature Methods
385 papers in training set
Top 2%
4.2%
50% of probability mass above
6
Bioinformatics
1204 papers in training set
Top 5%
3.9%
7
Proceedings of the National Academy of Sciences
2444 papers in training set
Top 18%
3.1%
8
Briefings in Bioinformatics
354 papers in training set
Top 3%
2.7%
9
Genome Research
468 papers in training set
Top 3%
2.4%
10
New Phytologist
346 papers in training set
Top 3%
2.3%
11
Nature Machine Intelligence
70 papers in training set
Top 2%
1.7%
12
Scientific Reports
3612 papers in training set
Top 57%
1.6%
13
Nucleic Acids Research
1281 papers in training set
Top 9%
1.6%
14
BMC Bioinformatics
457 papers in training set
Top 4%
1.5%
15
Genome Biology
637 papers in training set
Top 6%
1.5%
16
Methods in Ecology and Evolution
176 papers in training set
Top 1%
1.5%
17
Nature Ecology & Evolution
18 papers in training set
Top 0.2%
1.3%
18
Molecular Phylogenetics and Evolution
69 papers in training set
Top 0.7%
1.1%
19
Science
477 papers in training set
Top 7%
1.1%
20
Nature Biotechnology
172 papers in training set
Top 4%
1.0%
21
Nature
645 papers in training set
Top 9%
1.0%
22
Nature Computational Science
55 papers in training set
Top 1%
1.0%
23
NAR Genomics and Bioinformatics
242 papers in training set
Top 4%
0.9%
24
Cell Systems
201 papers in training set
Top 5%
0.8%
25
PLOS ONE
5266 papers in training set
Top 63%
0.8%
26
Nature Genetics
286 papers in training set
Top 5%
0.8%
27
BMC Genomics
406 papers in training set
Top 9%
0.8%
28
eLife
5828 papers in training set
Top 66%
0.8%
29
Molecular Ecology Resources
171 papers in training set
Top 2%
0.6%
30
PLOS Biology
486 papers in training set
Top 15%
0.6%