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NMRbox: TRD 3

• A probabilistic core as a coherent inference engine • PINE+ Core

• Extend functionality through the new core• PINE+: Assignment, use of structure data, RNA

• Reproducibility – “revisable executable documentation” • Side-by-side, reproducible, probabilistic and deterministic

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Why Bayes?

argmin Etotal = Eempirical + λEexperimentalBayes: Extremizes the log-likelihood. Consistent & extensible determination of parameters

Constrain: NOEs not distances. J’s not dihedrals etc.

Consistency + Extensibility Reproducibility

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What is PINE and PINE Core?

• PINE is the probabilistic Bayesian engine for • Data verification (LACS)• Secondary structure determination (PECAN)• Assignment (PISTACHIO)• Peak picking (HIFI)• Bayesian updating (PINE) • Bayesian updating + deterministic constraints (ADAPT-NMR)• RNA assignment (RNA-Pairs)

LACS PECAN PISTACHIO HI FI

LACSPECANPISTACHIO

LACSPECANPISTACHIO

HI FI

ADAPT-NMR

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Corollary

• In our view, Pine has been a highly successful probabilistic model. The inference core has proven to be very powerful – an excellent setting for building a structure determination protocol for:

• Repeatability and Reproducibility• Coexistence of probabilistic and deterministic paradigms• Extensibility to support new functions through plugins

• Additionally empowering:• Revisable executable documentation

• Document as you go, execute any time, reuse.

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PINE+

• PINE+ is the collection of applications • Containing a core probabilistic engine• The core will support all existing tools

• HIFI, PINE, PECAN, ADAPT-NMR, LACS, RNA-PAIRS

• And, New assignment tools• NOESY, RNA, Structure-based

• PINE+ will support probabilistic and deterministic approaches• PINE+ Will additionally enable reproducible results

• Playback of blocks or the entire project (repeatability)*• Edit & Replay of blocks or the entire project (reproducible)*• Template (reuse)

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Key Innovations

• The complete process of structure determination is captured and executed using one language, one environment, one paradigm, in open source form, using open technologies.

• As the user steps through structure determination steps, a living “executable document” is created – repeatability.

• “Blocks” of a structure determination “document” can be modified with new data or process – reproducibility.

• A “document” can be used as a “template”; replacing, or modifying blocks as needed – reuse.

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Transition, Transformation, Synergy

Current architecture

TRD 1: Virtual Machine

TRD 1: External applications & built-in applications

TRD 2: NMRSTAR

TRD 2: Workflow & Versions

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Impact

• Opportunity for • Enabling repeatable and reproducible structure determination• Empowering other packages with probabilistic functionality• Supporting side-by side deterministic and probabilistic tools• Creating end-to-end open source tools

• Built-in probabilistic functions for• Peak picking, backbone assignment, side-chain assignments,

secondary structure prediction, verification, NOESY assignment, RNA assignment, pipeline/network definition, scientific documentation, capture and replay, edit and execute.

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Progress to date

• Things under the hood• Environment • Protocol• Engine

• Demonstration• Interface• Desktop PINE• Executable document

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Progress in context

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Things under the hood

• Environment• High performance, dynamic, distributed, parallel, scientific computing

• Protocol• JSON for specification and exchange, Pandoc for data transformation

• Engine• Inference-as-a-service using a resource-oriented model• Simple (6 components) relation, learner, predictor, transformer, attribute, schema

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Demo

• Show interface and interaction

• Start a PINE job

• Display output of PINE

• Show block idea

• Show repeatability idea