Efficient visualization of chemical space
- 1Department of Chemistry, Quantum Theory Project, University of Florida Gainesville FL 32611 USA
Abstract
The concept of chemical space is critical in cheminformatics, medicinal chemistry, and machine learning applications. Despite this, the high dimensionality of molecular representations greatly complicates its sampling, analysis, and visualization. A popular approach to overcome problem is to project these representations to a “human-manageable” subspace, usually containing only two dimensions. Non-linear dimensionality reduction techniques are by far the preferred strategy, following the reasoning that their flexibility can accommodate any arbitrary distribution originally present in the high-dimensional space. However, this ignores the elevated computational cost of these methods and the difficulty in tuning their hyper-parameters. Here, we show that basic properties of the metrics used in the original space can be used to infer the shape of the chemical space, which in turns suggests an optimal strategy to project chemical information to lower dimensions. The key insight is to realize that no matter the set of molecules, the binary fingerprint representation evaluated under the Tanimoto metric can be considered to lie on a hyper-spherical surface. The smooth nature of this manifold indicates that we can use clustering in the original fingerprint representation to identify locally-dense sectors of chemical space, and selectively project them simply using linear (hyper-parameter free) methods, like principal component analysis. This approach surpasses non-linear techniques in several neighborhood preservation metrics, while only requiring a fraction of the computational cost. This pipeline is implemented in our N-Ary Mapping Interface (NAMI: https://github.com/mqcomplab/NAMI), which we tested in the visualization of tens of millions of molecules.
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BibTeX
@article{surendran2026efficient,
title = {{Efficient visualization of chemical space}},
author = {Akash Surendran and Krisztina Zsigmond and Lexin Chen and Ramón Alain Miranda-Quintana},
journal = {Chemical Science},
year = {2026},
month = sep,
doi = {10.1039/d6sc03716j},
url = {https://doi.org/10.1039/d6sc03716j},
note = {CC BY 3.0},
}
RIS
TY - JOUR
TI - Efficient visualization of chemical space
AU - Akash Surendran
AU - Krisztina Zsigmond
AU - Lexin Chen
AU - Ramón Alain Miranda-Quintana
PY - 2026
DA - 2026/09/11
JO - Chemical Science
DO - 10.1039/d6sc03716j
UR - https://doi.org/10.1039/d6sc03716j
AB - The concept of chemical space is critical in cheminformatics, medicinal chemistry, and machine learning applications. Despite this, the high dimensionality of molecular representations greatly complicates its sampling, analysis, and visualization. A popular approach to overcome problem is to project these representations to a “human-manageable” subspace, usually containing only two dimensions. Non-linear dimensionality reduction techniques are by far the preferred strategy, following the reasoning that their flexibility can accommodate any arbitrary distribution originally present in the high-dimensional space. However, this ignores the elevated computational cost of these methods and the difficulty in tuning their hyper-parameters. Here, we show that basic properties of the metrics used in the original space can be used to infer the shape of the chemical space, which in turns suggests an optimal strategy to project chemical information to lower dimensions. The key insight is to realize that no matter the set of molecules, the binary fingerprint representation evaluated under the Tanimoto metric can be considered to lie on a hyper-spherical surface. The smooth nature of this manifold indicates that we can use clustering in the original fingerprint representation to identify locally-dense sectors of chemical space, and selectively project them simply using linear (hyper-parameter free) methods, like principal component analysis. This approach surpasses non-linear techniques in several neighborhood preservation metrics, while only requiring a fraction of the computational cost. This pipeline is implemented in our N-Ary Mapping Interface (NAMI: https://github.com/mqcomplab/NAMI), which we tested in the visualization of tens of millions of molecules.
SN - 2041-6520
SN - 2041-6539
ER -