Portrait of Doruk Cakmakci

Doruk Cakmakci

doruk.cakmakci@mila.quebec
PhD - McGill University
Supervisor
Yue Li
Research Topics
Computational Biology
Deep Learning
Probabilistic Models
Website
Google Scholar
GitHub

Publications

DNA-aware evaluation and debiasing of sequence-to-function models
Doruk Cakmakci
Yue Li
MOTIVATION: Genome sequence-to-function (S2F) models are widely used to interpret base-resolution functional genomics assays. Most S2F model… (see more)s are trained and evaluated against observed counts and profile-shapes using statistical objectives and fidelity metrics. These choices are well motivated, but they are DNA-independent. At the same time, experimental measurements arise from DNA-dependent assays with distinct characteristics. This mismatch motivates a complementary DNA-aware evaluation of S2F-predicted and experimental functional genomic tracks. RESULTS: We study DNA-dependency of experimental and S2F-predicted tracks using track-conditional genome language models (cgLMs). cgLMs predict masked nucleotides from a conditioning track under controlled DNA visibility. Across ATAC-seq and TF ChIP-seq peaks from GM12878 and K562, cgLM-probing reveals a consistent masked DNA-decodability gap between many experimental and S2F-predicted tracks. In particular, single-task (e.g. BPNet) and multi-task (e.g. AlphaGenome) S2F-predicted tracks enabled cgLMs to recover masked nucleotides with significantly higher accuracy and confidence than matched experimental tracks. Analyses of nonpeak and dinucleotide-shuffled sequences show that this gap is not confined to peaks and is not captured by standard DNA-agnostic profile-shape fidelity metrics alone. ChromBPNet Tn5-denoised predictions were an exception and behaved closer to the experimental regime, suggesting that staged training may reduce the gap. We then convert this diagnostic into a critic-derived objective, DNA-dependency matching (DDM), using a frozen multi-headed cgLM critic. We introduce Critic-Guided Profile-Shape Editing (CGPSE), a preliminary post hoc debiasing framework for frozen S2F models. In GM12878 ATAC-seq, CGPSE partially reduces the masked DNA-decodability gap for AlphaGenome and BPNet predictions, while exposing a tradeoff with profile-shape fidelity. AVAILABILITY AND IMPLEMENTATION: https://github.com/li-lab-mcgill/dna-aware-s2f-eval.
2026-07-06
Bioinformatics (published)
doi.org
Single-nucleus chromatin accessibility profiling identifies cell types and functional variants contributing to major depression
Anjali Chawla
Doruk Cakmakci
Laura M. Fiori
Wenmin Zang
Malosree Maitra
Jennie Yang
Dariusz Żurawek
Gabriella Frosi
Reza Rahimian
Haruka Mitsuhashi
Maria Antonietta Davoli
MA Davoli
Ryan Denniston
Gary Gang Chen
Volodymyr Yerko
Deborah Mash
Kiran Girdhar
Schahram Akbarian
Naguib Mechawar
Matthew Suderman … (see 3 more)
Yuemei Li
Corina Nagy
Gustavo Turecki
2025-08-04
Nature Genetics (published)
doi.org
Differential Chromatin Architecture and Risk Variants in Deep Layer Excitatory Neurons and Grey Matter Microglia Contribute to Major Depressive Disorder
Anjali Chawla
Doruk Cakmakci
Wenmin Zhang
Malosree Maitra
Reza Rahimian
Haruka Mitsuhashi
MA Davoli
Jenny Yang
Gary Gang Chen
Ryan Denniston
Deborah Mash
Naguib Mechawar
Matthew Suderman
Yuemei Li
Corina Nagy
Gustavo Turecki
2023-10-02
bioRxiv (preprint)
doi.org