Appendix E — Model and Dataset Index

Canonical reference table for the major models, datasets, benchmarks, and infrastructure cited across the handbook. Organised by category. Evidence tier reflects the published-evidence weight, not the marketing or vendor-reported claims. DOI and official-source links are verified before inclusion.

Protein Structure Prediction

Model / Resource	Main Use	Evidence Tier	Source
AlphaFold 2	Single-chain protein structure prediction	Demonstrated	Jumper et al., 2021
RoseTTAFold	Open AlphaFold-2-class structure prediction	Demonstrated	Baek et al., 2021
ESMFold	MSA-free protein structure prediction	Demonstrated	Lin et al., 2023
AlphaFold 3	Biomolecular interaction structure prediction	Demonstrated; initial release restricted	Abramson et al., 2024
AlphaFold-Multimer	Protein complex structure prediction	Demonstrated (preprint)	Evans et al., 2021, preprint
OmegaFold	Single-sequence prediction (orphan and designed proteins)	Demonstrated (preprint)	Wu et al., 2022, preprint
Boltz-1	Open AlphaFold-3-class biomolecular interaction model	Demonstrated (preprint)	Wohlwend et al., 2024, preprint
Boltz-2	Open AF3-class with binding-affinity head	Demonstrated (preprint)	Passaro et al., 2025, preprint
Chai-1	Open AF3-class biomolecular interaction model	Demonstrated (preprint)	Chai Discovery et al., 2024, preprint
AlphaFold DB	Predicted protein structure database (>214M entries)	Demonstrated infrastructure	Varadi et al., 2024

Protein Language Models

Model	Main Use	Evidence Tier	Source
ESM-1b	Foundational protein language model (250M sequences)	Demonstrated	Rives et al., 2021
ESM-2	15B-parameter protein language model	Demonstrated	Lin et al., 2023
ESM3	Multimodal generative protein language model	Demonstrated for esmGFP	Hayes et al., 2025
ProtBERT / ProtTrans	BERT-style protein language model	Demonstrated baseline	Elnaggar et al., 2022
ProGen2	Autoregressive protein generation	Demonstrated	Nijkamp et al., 2023

Protein and Antibody Design

Model	Main Use	Evidence Tier	Source
RFdiffusion	Protein backbone generation	Demonstrated	Watson et al., 2023
ProteinMPNN	Inverse-folding sequence design	Demonstrated	Dauparas et al., 2022
LigandMPNN	Ligand-aware sequence design	Demonstrated	Dauparas et al., 2025
Chroma	Programmable generative protein model	Demonstrated	Ingraham et al., 2023
EvoDiff	Sequence-space diffusion	Demonstrated (preprint)	Alamdari et al., 2023, preprint
ProteinGenerator	Sequence-space diffusion for multistate and functional design	Demonstrated	Lisanza et al., 2024
EVOLVEpro	Few-shot active learning for protein activity optimization	Demonstrated	Jiang et al., 2025
COMPSS	Experiment-calibrated enzyme-design scoring	Demonstrated	Johnson et al., 2024
AlphaProteo	De novo binder generation	Reported (arXiv only, restricted code)	Zambaldi et al., 2024, preprint
RFantibody	De novo antibody design	Demonstrated	Bennett et al., 2026
IgFold	Antibody-specific structure prediction	Demonstrated	Ruffolo et al., 2023
AbLang	Antibody language model	Demonstrated	Olsen et al., 2022
Hie PLM evolution	Protein-language-model antibody affinity maturation	Demonstrated	Hie et al., 2024
Shanker structure-informed PLM	Protein and antibody complex optimization	Demonstrated	Shanker et al., 2024
Rosetta3	Classical protein design framework	Demonstrated baseline	Leaver-Fay et al., 2011

Single-Cell and Cellular AI

Model / Resource	Main Use	Evidence Tier	Source
scGPT	Single-cell foundation model	Demonstrated for representation; contested for perturbation	Cui et al., 2024
Geneformer	Single-cell foundation model	Demonstrated	Theodoris et al., 2023
scFoundation	Larger-scale scFM recipe	Demonstrated	Hao et al., 2024
scBERT	Earlier scFM baseline	Demonstrated	Yang et al., 2022
Nicheformer	Spatially aware single-cell and spatial-omics foundation model	Demonstrated	Tejada-Lapuerta et al., 2025
Novae	Graph-based spatial transcriptomics foundation model	Demonstrated	Blampey et al., 2025
SCimilarity	Cell-atlas-scale search	Demonstrated	Heimberg et al., 2025
GEARS	Transcriptional perturbation prediction	Demonstrated for bounded settings	Roohani et al., 2024
scGen	Perturbation transfer via VAE	Demonstrated	Lotfollahi et al., 2019
CPA	Compositional perturbation autoencoder	Demonstrated	Lotfollahi et al., 2023
Neural optimal transport	Counterfactual single-cell perturbation response modelling	Demonstrated	Bunne et al., 2023
Perturb-CITE-seq	Joint RNA and protein perturbation screens	Demonstrated data-generation method	Frangieh et al., 2021
Tabula Sapiens	Benchmark human cell atlas	Demonstrated infrastructure	Tabula Sapiens Consortium, 2022
CZ CELLxGENE Census	~100M curated single-cell observations	Demonstrated infrastructure	CZ CELLxGENE team, 2023, preprint
Cell Painting	High-content morphological profiling	Demonstrated protocol	Bray et al., 2016
CellProfiler	Open-source image analysis	Demonstrated infrastructure	Carpenter et al., 2006
SpatialData	Spatial omics data framework	Demonstrated infrastructure	Marconato et al., 2024
JUMP morphology maps	Matched and gene-expression perturbation morphology references	Demonstrated data layer	Chandrasekaran et al., 2024; Chandrasekaran et al., 2025

Histopathology, Microscopy, and Cryo-EM

Model / Resource	Main Use	Evidence Tier	Source
UNI	Computational pathology representation learning	Demonstrated	Chen et al., 2024
CONCH	Pathology visual-language representation	Demonstrated	Lu et al., 2024
Virchow	Whole-slide pathology representation and rare-cancer work	Demonstrated	Vorontsov et al., 2024
Prov-GigaPath	Whole-slide foundation model from real-world pathology data	Demonstrated	Xu et al., 2024
CHIEF	Cancer pathology diagnosis and prognosis foundation model	Demonstrated	Wang et al., 2024
MUSK	Vision-language pathology model for precision oncology	Demonstrated	Xiang et al., 2025
TITAN	Multimodal whole-slide and report-aligned foundation model	Demonstrated	Ding et al., 2025
HoVer-Net	Histology nuclei segmentation and classification	Demonstrated	Graham et al., 2019
Cellpose	Generalist cell segmentation	Demonstrated	Stringer et al., 2021
Cellpose3	Restoration-aware cell segmentation	Demonstrated	Stringer et al., 2025
StarDist	Star-convex cell and nuclei detection	Demonstrated	Schmidt et al., 2018
Segment Anything for Microscopy	Microscopy segmentation foundation model	Demonstrated	Archit et al., 2025
CARE	Fluorescence microscopy restoration	Demonstrated	Weigert et al., 2018
Noise2Void	Self-supervised denoising	Demonstrated	Krull et al., 2019
Deep-STORM	Super-resolution localization microscopy	Demonstrated	Nehme et al., 2018
ANNA-PALM	Accelerated super-resolution localization microscopy	Demonstrated	Ouyang et al., 2018
In-silico labeling	Label-free fluorescent-label prediction	Demonstrated	Christiansen et al., 2018
cryoSPARC	Cryo-EM structure-determination workflow	Demonstrated	Punjani et al., 2017
Topaz	Cryo-EM particle picking	Demonstrated	Bepler et al., 2019
crYOLO	Cryo-EM particle picking	Demonstrated	Wagner et al., 2019
CryoDRGN	Cryo-EM heterogeneous reconstruction	Demonstrated	Zhong et al., 2021
DynaMight	Cryo-EM continuous motion estimation	Demonstrated	Schwab et al., 2024
tomoDRGN	Cryo-ET subtomogram heterogeneity modelling	Demonstrated	Powell et al., 2024

Genome and Variant Models

Model	Main Use	Evidence Tier	Source
Evo	7B-parameter genome foundation model	Demonstrated	Nguyen et al., 2024
Evo 2	40B-parameter all-domains genome model	Demonstrated	Brixi et al., 2026
Nucleotide Transformer	Multi-species genome foundation model	Demonstrated	Dalla-Torre et al., 2025
GET	Transcription foundation model across human cell types	Demonstrated	Fu et al., 2025
Orthrus	Mature RNA foundation model	Demonstrated	Fradkin et al., 2026
Semantic design with Evo	Function-guided generated genes and SynGenome	Demonstrated	Merchant et al., 2026
GPN-MSA	Multispecies alignment DNA language model for variant effects	Demonstrated	Benegas et al., 2025
LucaOne	Unified nucleic-acid and protein language model	Demonstrated	He et al., 2025
ChatNT	Conversational agent for DNA, RNA, and protein tasks	Demonstrated	de Almeida et al., 2025
AlphaGenome	Regulatory variant prediction (megabase context)	Demonstrated	Avsec et al., 2026
Enformer	Long-range regulatory prediction	Demonstrated	Avsec et al., 2021
DeepSEA	Single-nucleotide chromatin impact	Demonstrated	Zhou and Troyanskaya, 2015
AlphaMissense	Proteome-wide missense pathogenicity	Demonstrated as research tool	Cheng et al., 2023
EVE	Evolutionary missense pathogenicity	Demonstrated	Frazer et al., 2021
ESM-1v	Zero-shot variant effect from language model	Demonstrated (preprint)	Meier et al., 2021, preprint
PrimateAI	Missense pathogenicity from primate population data	Demonstrated	Sundaram et al., 2018
SpliceAI	Splice-altering variant prediction	Demonstrated	Jaganathan et al., 2019
REVEL	Missense ensemble baseline	Demonstrated baseline	Ioannidis et al., 2016
CADD	Cross-variant ensemble baseline	Demonstrated baseline	Kircher et al., 2014
Disease-specific VEP model	Cardiac and regulatory variant contexts	Demonstrated	Zhan et al., 2025

Small Molecule and Drug Discovery

Model / Resource	Main Use	Evidence Tier	Source
REINVENT 4	Generative chemistry (RL on SMILES)	Demonstrated	Loeffler et al., 2024
DiffDock	Diffusion-based blind docking	Demonstrated (preprint, with PoseBusters caveat)	Corso et al., 2023, preprint
Pocket2Mol	Pocket-conditioned generation	Demonstrated (preprint)	Peng et al., 2022, preprint
Chemprop	Message-passing molecular property prediction	Demonstrated baseline	Yang et al., 2019
ADMET-AI	ADMET predictor over large libraries	Demonstrated	Swanson et al., 2024
ADMETlab 3.0	ADMET prediction platform	Demonstrated	Fu et al., 2024
Vina	Physics-based docking baseline	Demonstrated baseline	Trott and Olson, 2010
Connectivity Map L1000	Perturbational signature matching	Demonstrated infrastructure	Subramanian et al., 2017
DeepSynergy	Drug-combination synergy prediction	Demonstrated	Preuer et al., 2018
SynergyFinder 2.0	Multi-drug synergy visual analytics	Demonstrated infrastructure	Ianevski et al., 2020
TxGNN	Graph foundation model for zero-shot drug repurposing	Demonstrated for prioritization	Huang et al., 2024
Rentosertib	AI-discovered TNIK inhibitor in randomized Phase 2a testing	Demonstrated clinical signal; no approval	Xu et al., 2025

Autonomous Laboratories

System	Main Use	Evidence Tier	Source
Coscientist	LLM-planned autonomous chemistry	Demonstrated (Pd cross-coupling)	Boiko et al., 2023
Virtual Lab	Multi-agent biology research	Demonstrated (SARS-CoV-2 nanobodies)	Swanson et al., 2025
A-Lab	Autonomous inorganic materials	Demonstrated platform; novelty claims debated	Szymanski et al., 2023
Ada	Self-driving thin-film materials	Demonstrated	MacLeod et al., 2020
ChemOS	Workflow orchestration	Demonstrated infrastructure	Roch et al., 2020
Mobile robotic chemist	Untethered chemistry robot	Demonstrated	Burger et al., 2020
ChemCrow	LLM agent with chemistry tools	Demonstrated	M. Bran et al., 2024
CellVoyager	Autonomous single-cell analysis agent	Demonstrated	Alber et al., 2026
Adam	First closed-loop robot scientist (functional genomics)	Demonstrated (historical)	King et al., 2009
PyLabRobot	Hardware-agnostic liquid-handling interface	Demonstrated infrastructure	Wierenga et al., 2023
SBOL 3	Structured language for synthetic biology designs	Demonstrated standard	Baig et al., 2020

Benchmarks and Evaluation

Benchmark	Domain	Source
CASP	Protein structure prediction (biennial blinded)	Kryshtafovych et al., 2024
CAMEO	Continuous structure-prediction evaluation	CAMEO, 2026
PoseBusters	Docking pose validity	Buttenschoen et al., 2024
MoleculeNet	Molecular ML benchmark (scaffold splits)	Wu et al., 2018
Therapeutics Data Commons	Multi-task therapeutic discovery	Huang et al., 2022
scIB	Single-cell integration benchmark	Luecken et al., 2022
OpenProblems	Single-cell multi-task benchmark	Luecken et al., 2025
Virtual Cell Challenge	Perturbation-response benchmark for virtual-cell models	Roohani et al., 2025
DOME framework	Reporting standard for supervised ML in biology	Walsh et al., 2021

Critical-Evaluation References

These independent evaluations bound how much weight to give published headline numbers:

Critique	Finding	Source
Ahlmann-Eltze et al.	Linear baselines compete with deep methods on single-cell perturbation prediction	Ahlmann-Eltze et al., 2025
Boiarsky et al.	Independent re-evaluation of scFM finds smaller-than-reported gains	Boiarsky et al., 2024
PoseBusters	Low-RMSD docking poses fail physical and chemical validity	Buttenschoen et al., 2024

Data and Infrastructure

Resource	Main Use	Source
PDB	Experimental macromolecular structures	wwPDB, 2026
AlphaFold DB	Predicted protein structures (>214M)	AlphaFold Protein Structure Database, 2026
ESM Metagenomic Atlas	Predicted metagenomic protein structures	ESM Metagenomic Atlas, 2026
ChEMBL	Curated bioactivity database	Zdrazil et al., 2024
PubChem	Chemical substance, compound, and assay database	Kim et al., 2023
Open Targets	Target-disease evidence integration	Ochoa et al., 2021
Human Cell Atlas	Reference cell atlas	Regev et al., 2017

Biomedical Knowledge and Literature AI

Model / Resource	Main Use	Evidence Tier	Source
BioBERT	Biomedical text mining	Demonstrated for text-mining benchmarks	Lee et al., 2020
PubMedBERT	Biomedical language representation	Demonstrated for biomedical NLP benchmarks	Gu et al., 2022
SciBERT	Scientific-text representation	Demonstrated for scientific NLP benchmarks	Beltagy et al., 2019
SemMedDB	Literature-mined semantic predications	Demonstrated infrastructure	Kilicoglu et al., 2012
Hetionet	Drug-repurposing knowledge graph	Demonstrated graph resource	Himmelstein et al., 2017
PrimeKG	Precision-medicine knowledge graph	Demonstrated graph resource	Chandak et al., 2023
Open Targets Platform	Target-disease evidence integration	Demonstrated infrastructure	Ochoa et al., 2021
BioCypher	Schema-driven biomedical knowledge representation	Demonstrated infrastructure	Lobentanzer et al., 2023

Programs and Regulatory References

Program	Scope	Source
NIH Bridge2AI	AI-ready biomedical data and workforce	NIH Common Fund Bridge2AI, 2026
ARPA-H IGoR	AI-supported biomedical research infrastructure	ARPA-H IGoR, 2026
CZI Virtual Cells Platform	Cell foundation model infrastructure	CZI, 2026
FDA AI/ML in drug development	Regulatory framing for AI in medicines	FDA, 2026
FDA Real-World Evidence Program	Regulatory framing for RWE use in drug development	FDA, 2026
FDA Biomarker Qualification Program	Biomarker context-of-use qualification	FDA, 2026
FDA PAT framework	Pharmaceutical manufacturing process measurement and control	FDA, 2004
EMA reflection paper on AI	EU regulatory framing for AI in medicinal lifecycle	EMA, 2024

Biomanufacturing References

Resource	Main Use	Source
Machine learning in bioprocess development	Review of ML applications in strain engineering, process development, scale-up, monitoring, and control	Helleckes et al., 2023
ML-based bioprocess optimisation review	Review of optimisation, monitoring, and control systems	Mondal et al., 2023
Digital twins in biopharma manufacturing	Digital-twin literature review	Chen et al., 2020
Ginkgo Bioworks	Biofoundry and autonomous-lab company context	Ginkgo Bioworks, 2026
Cytiva	Bioprocess equipment and life-sciences infrastructure context	Cytiva, 2026
Sartorius	Bioprocess and laboratory infrastructure context	Sartorius, 2026
Resilience	Biomanufacturing CDMO context	Resilience, 2026

Real-World Evidence and Biomarker Platforms

Platform	Main Use	Source
Tempus	Clinical and molecular data platform	Tempus, 2026
Flatiron Health	Oncology real-world data infrastructure	Flatiron Health, 2026
Komodo Health	Real-world data analytics for life sciences	Komodo Health, 2026
Datavant/Aetion	Health data collaboration and RWE analytics context	Datavant, 2026

Related Resources

• References: Master citation list with topic organisation.
• Glossary: Definitions of terminology.
• Quick Reference: All Chapter Summaries: TL;DR callouts from every chapter.