Zhengyi Chen

Statistical Pharmacology via Kakutani Dichotomy IV: KMS Inverse-Temperature Criticality β_c = 1, Pocket-to-Distal Tail Allostery, and the Four-Quadrant Ligand Classification

This is the fourth paper of the series Statistical Pharmacology via Kakutani Dichotomy, which transports the tail-event phase transition of Localized Bost–Connes systems (R. Chen, DOI 10.5281/zenodo.22883179) to the statistical geometry of protein conformational ensembles. Papers...

Spectral Kakutani–Feldman–Hájek Criticality of Correlated Conformational Modes: Mode Amplitude Perturbation, Iso-Spectral Givens Rotation, and Tail-Increment Finite-Size Elimination

This is the third paper of the series "Statistical Pharmacology via Kakutani Dichotomy". Paper II (DOI 10.5281/zenodo.23012217) decomposed the covariance part of the correlated Kakutani index of two Gaussian conformational ensembles into a commuting amplitude part and a non-commu...

When does sequence order matter? An information-theoretic taxonomy of biological representation tasks and the limits of local encoding

Biological sequence models range from amino acid composition and k-mer counters to convolutional networks and billion-parameter language models. When is a local representation sufficient, and when is global order indispensable? This closing paper of an eight-part series answers t...

When does sequence order matter? An information-theoretic taxonomy of biological representation tasks and the limits of local encoding

Biological sequence models range from amino acid composition and k-mer counters to convolutional networks and billion-parameter language models. When is a local representation sufficient, and when is global order indispensable? This closing paper of an eight-part series answers t...

Phenotypic insufficiency of local protein representations: fibre-preserving rearrangements of human C2H2 zinc-finger arrays reorder DNA-recognition residues under an invariant 25-spectrum

A protein representation built from local sequence statistics assigns the same vector to all sequences with the same multiset of k-mers, the spectral fibre. Whether this blind spot matters depends on the phenotype. For C2H2 zinc-finger proteins, whose fingers read DNA in order, i...

Symmetry-constrained spectral fibres: reverse-complement group actions on double-stranded DNA and the fibres of circular molecular fingerprints

A representation that depends on an object only through its local content is constant on the object's spectral fibre, the set of objects with the same multiset of local pieces. This paper treats two settings in which a symmetry enters. Double-stranded DNA. Reverse complementation...

FibreBench: stress-testing protein sequence encoders against exact combinatorial spectral invariants

Protein representation models are usually evaluated on test sets split by sequence identity. Such splits cannot reveal what an architecture is unable to distinguish by construction. FibreBench is a benchmark built from an exact invariant instead. Each test pair consists of a huma...

Biologically reachable spectral fibres: repeat shuffling, copy ambiguity and the scarcity of cryptic pathogenic missense variants in ClinVar

A protein sequence encoder that depends only on k-mer statistics is blind to the rearrangements that preserve them: the spectral fibre of the protein. Most members of a fibre are not proteins that evolution or disease could produce. We ask which part of the fibre is biologically...

Biologically reachable spectral fibres: repeat shuffling, copy ambiguity and the scarcity of cryptic pathogenic missense variants in ClinVar

A protein sequence encoder that depends only on k-mer statistics is blind to the rearrangements that preserve them: the spectral fibre of the protein. Most members of a fibre are not proteins that evolution or disease could produce. We ask which part of the fibre is biologically...