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Master Reference List

All publications, datasets, and resources referenced across the OpenWorm documentation and Design Documents. The Description column indicates which Design Documents cite each reference.

Core OpenWorm Publications

Citation Journal Year Description
Sarma et al. 2018 Phil Trans R Soc B 373:20170382 2018 OpenWorm: overview and recent advances in integrative biological simulation of C. elegans. DD011
Gleeson et al. 2018 Phil Trans R Soc B 373:20170379 2018 c302: a multiscale framework for modelling the nervous system of C. elegans. DD001
Sarma et al. 2016 F1000Research 5:1946 2016 Unit testing, model validation, and biological simulation. DD010, DD013, DD021

Connectome & Neural Wiring

Citation Journal Year Description
White et al. 1986 Phil Trans R Soc B 314:1-340 1986 The original C. elegans connectome — "The Mind of a Worm". DD006, DD010, DD018, DD019, DD020
Varshney et al. 2011 PLoS Comput Biol 7:e1001066 2011 Updated connectome with corrected synapse counts. DD020
Cook et al. 2019 Nature 571:63-71 2019 Whole-animal connectome of adult hermaphrodite and male — primary connectome for OpenWorm. DD001, DD002, DD003, DD006, DD008, DD010, DD014, DD018, DD019, DD020, DD024
Witvliet et al. 2021 Nature 596:257-261 2021 Developmental connectomes across 8 stages (L1 → adult). DD001, DD004, DD006, DD008, DD014, DD020
Brittin et al. 2021 Nature 591:105-110 2021 Contact-area-based connectome weighting. DD020
Wang et al. 2024 eLife 13:RP95402 2024 Neurotransmitter identity for every synapse. DD001, DD006, DD020
Yim et al. 2024 Nat Commun 15:1546 2024 Comparative connectomics of dauer. DD014, DD020
Bentley et al. 2016 PLoS Comput Biol 12:e1005283 2016 Multilayer connectome of C. elegans (synaptic + gap junction + neuropeptide layers). DD006
Bargmann & Marder 2013 Nat Methods 10:483-490 2013 From the connectome to brain function — connection topology is necessary but not sufficient. DD001

Whole-Brain Imaging & Neural Dynamics

Citation Journal Year Description
Randi et al. 2023 Nature 623:406-414 2023 Whole-brain calcium imaging — primary data for Tier 2 validation. Validation, DD005, DD006, DD008, DD010, DD017, DD020, DD024
Kato et al. 2015 Cell 163:656-669 2015 Global brain dynamics embed the motor command sequence of C. elegans — PCA of whole-brain dynamics. DD001, DD010
Atanas et al. 2022 bioRxiv 2022.11.11.516186 2022 Brain-wide representations of behavior spanning multiple timescales and states. DD006

Neuropeptide & Neuromodulatory Signaling

Citation Journal Year Description
Ripoll-Sanchez et al. 2023 Neuron 111:3570-3589 2023 Neuropeptide connectome — 31,479 peptide-receptor interactions. DD006, DD008, DD010, DD020
Li et al. 1999 Brain Res 848:26-34 1999 FMRFamide-related neuropeptide gene family in C. elegans. DD006, DD010
Rogers et al. 2003 Nat Neurosci 6:1178-1185 2003 FLP peptide loss-of-function phenotypes. DD006, DD010
Choi et al. 2013 Neuron 78:869-880 2013 PDF-1 neuropeptide modulates arousal state. DD006
Pereira et al. 2015 eLife 4:e12432 2015 Cellular and regulatory map of the cholinergic nervous system of C. elegans. DD006, DD010
Beets et al. 2022 eLife 12:e81548 2022 System-wide mapping of neuropeptide-GPCR interactions in C. elegans. DD006
Flavell et al. 2020 Genetics 216:315-332 2020 Behavioral states in C. elegans. DD006, DD024
Marder et al. 2014 Annu Rev Neurosci 37:329-346 2014 Neuromodulation of circuits with variable parameters. DD015

Single-Cell Electrophysiology (Tier 1 Validation)

Citation Journal Year Description
Goodman et al. 1998 Neuron 20:763-772 1998 Active currents regulate sensitivity and dynamic range in C. elegans neurons — evidence for graded potentials. DD001, DD002, DD005, DD024
Goodman et al. 2002 Nature 415:1039-1042 2002 Touch receptor whole-cell patch-clamp — primary Tier 1 data for ALM, AVM, PLM. DD010, DD019, DD024
O'Hagan et al. 2005 Nat Neurosci 8:43-50 2005 MEC-4 DEG/ENaC channel kinetics in touch neurons. DD010, DD019, DD024
Suzuki et al. 2003 Neuron 39:1005-1017 2003 In vivo calcium imaging of mechanosensory neurons (ALM, AVM, PLM). DD010
Chalasani et al. 2007 Nature 449:63-71 2007 AWC olfactory neuron calcium imaging, TAX-2/TAX-4 channel characterization. DD005, DD010
Lindsay et al. 2011 Nat Commun 2:306 2011 AVA command interneuron whole-cell recordings — graded potential dynamics. DD010
Liu et al. 2018 Cell 175:57-70 2018 AWA olfactory neurons fire all-or-none action potentials; supplementary RIM/AIY electrophysiology. DD001, DD010
Mellem et al. 2002 Neuron 36:933-944 2002 Interneuron electrophysiology — AVA, AVD, AVB recordings. DD010
Hendricks et al. 2012 Nature 487:99-103 2012 Compartmentalized calcium dynamics in a C. elegans interneuron — evidence for spatially compartmentalized signaling within neurons. DD001
Nicoletti et al. 2019 PLoS ONE 14:e0218738 2019 Biophysical modeling of C. elegans neurons: Single ion currents and whole-cell dynamics of AWCon and RMD. DD001
Leifer et al. 2011 Nat Methods 8:147-152 2011 Optogenetic manipulation of neural activity in freely moving C. elegans. DD010
Zheng et al. 1999 Neuron 24:347-361 1999 GLR-1 ionotropic glutamate receptor in locomotion — B-class motor neuron control of forward movement. DD010

Gene Expression & Transcriptomics

Citation Journal Year Description
Taylor et al. 2021 Cell 184:4329-4347 2021 CeNGEN — single-cell transcriptome atlas of 128 neuron classes. DD005, DD006, DD010
Packer et al. 2019 Science 365:eaax1971 2019 Embryonic single-cell RNA-seq atlas. DD005, DD008
Yemini et al. 2021 Cell 184:272-288 2021 NeuroPAL: Multicolor atlas for whole-brain neuronal identification in C. elegans. DD005
Alon et al. 2021 Science 371:eaax2656 2021 Expansion sequencing: spatially precise in situ transcriptomics in intact biological systems. DD001, DD005
Shaib et al. 2023 Nat Biotechnol 2023 C. elegans-optimized expansion microscopy — synapse-level molecular identity with 20-fold expansion. DD001, DD005

Muscle & Body Physics

Citation Journal Year Description
Boyle & Cohen 2008 Biosystems 94:170-181 2008 Muscle model with calcium-force coupling — basis for DD002. DD001, DD002, DD003, DD005, DD017
Müller et al. 2003 Proc. ACM SIGGRAPH/Eurographics SCA pp. 154-159 2003 Particle-based fluid simulation for interactive applications — SPH kernel functions. DD003
Solenthaler & Pajarola 2009 ACM Trans Graphics 28(3):40 2009 Predictive-Corrective Incompressible SPH (PCISPH) — pressure solver used in Sibernetic. DD003
Bouaziz et al. 2014 ACM Trans Graphics 33:154 2014 Projective Dynamics: fusing constraint projections for fast simulation — FEM alternative to SPH. DD003
Wen et al. 2012 Neuron 76:750-761 2012 Proprioceptive coupling within motor neurons drives undulatory locomotion in C. elegans. DD019, DD023

Touch & Mechanosensation

Citation Journal Year Description
Chalfie et al. 1985 J Neurosci 5:956-964 1985 Discovery of gentle touch response circuit. Validation, DD010, DD019, DD024
O'Hagan et al. 2005 Nat Neurosci 8:43-50 2005 MEC-4 channel electrophysiology (DEG/ENaC mechanotransduction). DD010, DD019, DD024
Wicks et al. 1996 J Neurosci 16:4017-4031 1996 Tap withdrawal circuit — anterior vs. posterior discrimination. DD019
Goodman et al. 2002 Nature 415:1039-1042 2002 Touch receptor electrophysiology. DD010, DD019, DD024
Suzuki et al. 2003 Neuron 39:1005-1017 2003 In vivo calcium imaging of mechanosensory neurons. DD010
Hilliard et al. 2005 EMBO J 24:63-72 2005 In vivo imaging of ASH nociceptor neurons — calcium response and adaptation to chemical repellents. DD010
Chalasani et al. 2007 Nature 449:63-71 2007 Chemosensory transduction in AWC neurons. DD005, DD010

Pharynx & Feeding

Citation Journal Year Description
Raizen & Avery 1994 Neuron 12:483-495 1994 Electropharyngeogram (EPG) recordings — pharyngeal validation data. DD007, DD010, DD024
Avery & Horvitz 1989 Neuron 3:473-485 1989 Pharyngeal pumping continues after laser killing of the pharyngeal nervous system. DD007, DD010

Intestine & Defecation

Citation Journal Year Description
Thomas 1990 Genetics 124:855-872 1990 Defecation motor program timing (50s cycle). DD009, DD024
Dal Santo et al. 1999 Cell 98:757-767 1999 Cell-autonomous IP3/calcium oscillations in intestinal cells. DD009
Teramoto & Iwasaki 2006 Cell Calcium 40:319-327 2006 Intestinal calcium waves coordinate a behavioral motor program. DD009

Egg-Laying & Reproductive Circuit

Citation Journal Year Description
Trent et al. 1983 Genetics 104:619-647 1983 145 egg-laying defective (Egl) mutants, 4 pharmacological classes. DD010, DD018
Waggoner et al. 1998 Neuron 21:203-214 1998 Serotonin pharmacology of egg-laying — two-state behavioral model. DD018
Schafer 2006 WormBook 2006 Egg-laying comprehensive review. DD018
Zhang et al. 2008 Curr Biol 18:1445-1455 2008 Self-regulating feed-forward circuit controlling egg-laying behavior. DD018
Sun & Bhatt 2010 BMC Syst Biol 4:81 2010 Computational model of egg-laying circuit temporal pattern generation. DD018
Collins & Koelle 2013 J Neurosci 33:761-775 2013 UNC-103 ERG potassium channel in vulval muscles — two-state excitability mechanism. DD010, DD018
Collins et al. 2016 eLife 5:e21126 2016 Calcium imaging of egg-laying circuit — two-state behavioral pattern. DD018, DD024
Brewer et al. 2019 PLoS Genet 15:e1007896 2019 Tyramine/octopamine signaling in egg-laying. DD018
Ravi et al. 2020 J Neurosci 40:7475-7488 2020 Expression, function, and pharmacological analysis of all 26 neurotransmitter GPCRs in C. elegans. DD018
Kopchock et al. 2021 J Neurosci 41:3635-3650 2021 VC neurons are mechanically activated motor neurons in the egg-laying circuit. DD018
Collins & Bhatt 2022 Genetics 221:iyac084 2022 Serotonin signals through Gαq/Trio/DAG in egg-laying circuit. DD018

Behavioral Analysis & Neuroethology

Citation Journal Year Description
Schafer 2005 Curr Biol 15:R723-R729 2005 Deciphering the neural and molecular mechanisms of C. elegans behavior. DD021
Yemini et al. 2013 Nat Methods 10:877-879 2013 Schafer lab behavioral feature database — primary Tier 3 validation data. Validation, DD010, DD021, DD024
Brown et al. 2013 PNAS 110:791-796 2013 A dictionary of behavioral motifs reveals clusters of genes affecting locomotion. DD021
Berman et al. 2014 J R Soc Interface 11:20140672 2014 Mapping the stereotyped behaviour of freely moving fruit flies — behavioral embedding methods. DD010
Javer et al. 2018 Nat Methods 15:645-646 2018 Tierpsy Tracker — multi-worm behavioral tracking. DD021
Datta et al. 2019 Neuron 104:11-24 2019 Computational neuroethology: a call to action. DD010
Pereira TD et al. 2022 Nat Methods 19:486-495 2022 SLEAP: deep learning system for multi-animal pose estimation. DD010

Chemotaxis & Sensory Processing

Citation Journal Year Description
Pierce-Shimomura et al. 1999 J Neurosci 19:9557-9569 1999 Fundamental role of pirouettes in C. elegans chemotaxis — biased random walk strategy. DD022
Iino & Yoshida 2009 J Neurosci 29:5370-5380 2009 Parallel use of two behavioral mechanisms for NaCl chemotaxis. DD022

Anatomy & 3D Atlas

Citation Journal Year Description
Long et al. 2009 Nat Methods 6:667-672 2009 3D nuclear positions atlas (357 nuclei, L1 larva). DD004, DD006

Neural Circuit Variability & Parameter Fitting

Citation Journal Year Description
Prinz et al. 2004 Nat Neurosci 7:1345-1352 2004 Similar network activity from disparate circuit parameters. FAQ
Achard & De Schutter 2006 PLoS Comput Biol 2:e94 2006 Complex parameter landscape for a complex neuron model — the solution space approach. FAQ
Marder & Taylor 2011 Nat Rev Neurosci 12:563-574 2011 Multiple models to capture the variability in biological neurons and networks. FAQ
Kawano et al. 2011 Neuron 72:572-586 2011 An imbalancing act: gap junctions reduce backward motor circuit activity to bias C. elegans for forward locomotion. DD015

Reservoir Computing & Network Computation

Citation Journal Year Description
Yan et al. 2024 Nat Commun 15:5765 2024 Reservoir computing in biological neural networks — primary motivation for DD026. DD026
Jaeger 2001 GMD Report 148 2001 The "echo state" approach to analysing and training recurrent neural networks — original echo state network paper defining ESP and RC framework. DD026
Maass et al. 2002 Neural Computation 14:2531-2560 2002 Real-time computing without stable states — liquid state machines (RC for biological spiking networks). DD026
Lukoševičius & Jaeger 2009 Computer Science Review 3:127-149 2009 Reservoir computing approaches to recurrent neural network training — comprehensive RC review (memory capacity, separation property). DD026

Computational Methods & Machine Learning

Citation Journal Year Description
Cannon et al. 2014 Front Neuroinform 8:79 2014 LEMS: a language for expressing complex biological models — underpinning NeuroML 2. DD001
Linka et al. 2023 Acta Biomater 2023 Automated model discovery using constitutive artificial neural networks — RNN approach for inferring biophysical parameters. DD001
Zhao et al. 2024 Nat Comp Sci 4:978-990 2024 MetaWorm: integrative data-driven C. elegans brain-body-environment simulation — key related work. Validation, Full History, DD001, DD003, DD010, DD017, DD020, DD022
Chen et al. 2018 NeurIPS 2018 2018 Neural Ordinary Differential Equations — foundational differentiable ODE solvers. DD017
Rackauckas et al. 2020 arXiv:2001.04385 2020 Universal Differential Equations for Scientific Machine Learning — hybrid mechanistic-ML theory. DD017
Jumper et al. 2021 Nature 596:583-589 2021 AlphaFold: highly accurate protein structure prediction — used for ion channel kinetics pipeline. DD017, DD025
Lin et al. 2023 Science 379:1123-1130 2023 ESM2/ESM3: evolutionary-scale protein structure prediction with a language model. DD017, DD025
Zheng et al. 2025 Microsoft Research 2025 BioEmu-1: protein conformational ensembles at 100,000x MD speed — key enabler for ion channel dynamics prediction. DD025
Wohlwend et al. 2025 GitHub 2025 Boltz-2: open-source, single-GPU protein structure prediction matching AlphaFold 3 accuracy. DD025
Karr et al. 2012 Cell 150:389-401 2012 A Whole-Cell Computational Model Predicts Phenotype from Genotype — first complete intracellular simulation (28 submodels, 525 genes, M. genitalium). Precedent for Phase 5 intracellular signaling. Phase Roadmap
Karr 2014 Stanford University (PhD dissertation) 2014 Development and Application of Whole-Cell Computational Models for Science and Engineering — identified parameter curation bottleneck and cross-species transfer limitations. Phase Roadmap
Kochkov et al. 2024 Nature 632:1060-1066 2024 Neural General Circulation Models for weather and climate — precedent for learned surrogates in physical simulation. DD017

Philosophical Foundations

Citation Journal Year Description
Machamer et al. 2000 Philos Sci 67:1-25 2000 Thinking about Mechanisms — biological understanding requires identifying organized systems of entities and activities. Background
Pearl 2000 Cambridge University Press 2000 Causality: Models, Reasoning, and Inference — causal models vs. statistical models. Background
Chalmers 2006 Oxford University Press 2006 "Strong and Weak Emergence" — whether higher-level properties are deducible from lower-level laws. Background
Haspel et al. 2023 arXiv [q-bio.NC] 2308.06578 2023 To reverse engineer an entire nervous system — observational and perturbational completeness. DD001, DD010, DD017, Background
Pearl & Mackenzie 2018 Basic Books (ISBN: 978-0465097609) 2018 The Book of Why: The New Science of Cause and Effect. Validation, DD010, DD024, Background
Rosen 1991 Columbia University Press (ISBN: 978-0231075640) 1991 Life Itself: A Comprehensive Inquiry Into the Nature, Origin, and Fabrication of Life — causal loop philosophy. DD001

Online Datasets & Resources

Resource URL Description Used In
CeNGEN cengen.org Single-cell transcriptome atlas of 128 C. elegans neuron classes DD005, DD006, DD010
WormAtlas wormatlas.org Anatomical atlas, cell descriptions, EM images, Slidable Worm DD004, DD007, DD008, DD014.1
WormBase wormbase.org Gene annotation, cell ontology (WBbt), phenotype data DD004, DD008, DD014.1
Schafer Lab Database wormbehavior.mrc-lmb.cam.ac.uk Behavioral feature database for N2 and mutant strains DD010, DD021
ConnectomeToolbox github.com/openworm/ConnectomeToolbox Canonical API for all connectome datasets (cect) DD006, DD008, DD010, DD020
open-worm-analysis-toolbox github.com/openworm/open-worm-analysis-toolbox Movement analysis and Tier 3 behavioral validation DD021
OpenWorm Docker github.com/openworm/OpenWorm Meta-repository and simulation stack DD013
AlphaFold Protein Structure Database alphafold.ebi.ac.uk Predicted protein structures for ion channels DD017, DD025

How References Are Used

OpenWorm validates its simulation against experimental data at four tiers (DD010):

Tier What's Validated Key Data Sources
Tier 1 Single-cell electrophysiology Goodman et al. 1998, Goodman et al. 2002 (touch neurons), O'Hagan et al. 2005 (MEC-4 channels), Chalasani et al. 2007 (AWC), Lindsay et al. 2011 (AVA), Liu et al. 2018 (RIM)
Tier 2 Circuit functional connectivity Randi et al. 2023
Tier 3 Behavioral kinematics Yemini et al. 2013, Schafer Lab Database
Tier 4 Causal/interventional Chalfie et al. 1985, Pearl & Mackenzie 2018