Transcript schema-api-part1 - Bioinformatics Research Group at SRI

Computing with Pathway/Genome
Databases
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 Aprox
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presentation time: 1.5 hrs
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Overview
 Summary
of Pathway Tools data access
mechanisms and formats
 Pathway
Tools APIs
 Overview
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of Pathway Tools schema
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Motivations to Understanding Schema
 When
writing complex queries to PGDBs, those
queries must refer to classes and slots within the
schema
 Queries using Lisp, Perl, Java APIs
 Queries using Structured Advanced Query Form
 Queries using BioVelo
 Find
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all monomers longer than 1,000 amino acids
 (loop for g in (get-class-all-instances ‘|Genes|)
when (< 1000 (abs (- (get-slot-value g ‘left-end-position)
(get-slot-value g ‘right-end-position)
))
collect (get-slot-value
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Bioinformatics g ‘product) )
More Information
 Pathway
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http://bioinformatics.ai.sri.com/ptools/
PTools APIs: http://brg.ai.sri.com/ptools/ptools-resources.html
Web services: http://biocyc.org/web-services.shtml
 Guide

Tools Web Site, Tutorial Slides
to the Pathway Tools Schema
http://biocyc.org/schema.shtml
 Curator's
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Guide
http://bioinformatics.ai.sri.com/ptools/curatorsguide.pdf
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References
 Ontology
Papers section of
http://biocyc.org/publications.shtml
 "An Evidence Ontology for use in Pathway/Genome
Databases"
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"An ontology for biological function based on molecular
interactions"
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"Representations of metabolic knowledge: Pathways"
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"Representations of metabolic knowledge"
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Data Exchange
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APIs: Lisp API, Java API, and Perl API
 Read and modify access
Web services
Cyclone
Export to files
 BioPAX Export
Biopax.org
 Export PGDB genome to Genbank format
 Export entire PGDB as column-delimited and attribute-value file formats
 Export PGDB reactions as SBML -- sbml.org
 Import/Export of Pathways: between PGDBs
 Import/Export of Selected Frames, for Spreadsheets
 Import/Export of Compounds as Molfile, CML
BioWarehouse : Loader for Flatfiles, SQL access
 http://bioinformatics.ai.sri.com/biowarehouse/
 BMC Bioinformatics 7:170 2006
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Pathway Tools Ontology / Schema
 Ontology
classes: 1621
 Datatype classes: Define objects from genomes to pathways
 Classification systems for pathways, chemical compounds,
enzymatic reactions (EC system)
 Protein Feature ontology
 Controlled vocabularies:


Cell Component Ontology
Evidence codes
 Comprehensive
set of 279 attributes and
relationships
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High-Level Classes in the Pathway
Tools Ontology

Chemicals
Polymer-Segments
Protein-Features
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Organisms
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Reactions
Enzymatic-Reactions
Pathways
Regulation
-- Biochemical reactions
-- Link enzymes to reactions they catalyze
-- Metabolic and signaling pathways
-- Regulatory interactions
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CCO
Evidence
Gene-Ontology-Terms
-- Cell Component Ontology
-- Evidence ontology
-- GO
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Growth-Observations
-- Observations of growth of organism
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Notes
Organizations, People
Publications
-- Timestamped, person-stamped notes
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-- All molecules
-- Regions of polymers
-- Features on proteins
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Navigating the Schema
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Use GKB Editor to Inspect the
Pathway Tools Ontology
 GKB
Editor = Generic Knowledge Base Editor
 Type in Navigator window: (GKB)
or
 [Right-Click] Edit->Ontology Editor
 View->Browse
Class Hierarchy
 [Middle-Click] to expand hierarchy
 To view classes or instances, select them and:
 Frame -> List Frame Contents
 Frame -> Edit Frame
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Use the SAQP to Inspect the Schema
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Pathway Tools Schema
 Guide
to the Pathway Tools Schema
 Schema
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overview diagram
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Principal Classes

Class names are capitalized, plural, separated by dashes
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Genetic-Elements, with subclasses:
 Chromosomes
 Plasmids
Genes
Transcription-Units
RNAs
 rRNAs, snRNAs, tRNAs, Charged-tRNAs
Proteins, with subclasses:
 Polypeptides
 Protein-Complexes
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Principal Classes
 Reactions,
with subclasses:
 Transport-Reactions
 Enzymatic-Reactions
 Pathways
 Compounds-And-Elements
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Principal Classes
 Regulation
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Slot Links
TCA Cycle
in-pathway
Succinate + FAD = fumarate + FADH2
reaction
Enzymatic-reaction
catalyzes
Succinate dehydrogenase
component-of
Sdh-flavo
Sdh-Fe-S
Sdh-membrane-1
Sdh-membrane-2
product
sdhA
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sdhB
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sdhC
sdhD
Programmatic Access to BioCyc

Common LISP
•
Native language of Pathway Tools
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Interactive & Mature Environment
•
Full Access to the Data & Many Utility Functions
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Source code is available for academics
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PerlCyc
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API of Functions, Exposed to Perl
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Communication through UNIX Socket
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JavaCyc
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API of Functions, Exposed to Java
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Communication through UNIX Socket
•
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Cyclone
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Cyclone
 Developed
by Schachter and colleagues from
Genoscope
 http://nemo-cyclone.sourceforge.net/archi.php
 Cyclone
is a Java-based system that:
 Extracts data from a Pathway Tools PGDB
 Converts it to an XML schema
 Maps the data to Java objects and to a relational database
 Changes made to the data on the Java side can be
committed back to a Pathway Tools PGDB
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Lisp API
 Accessible
whenever you start Pathway Tools
with the –lisp argument
 Lisp queries evaluate against the running
Pathway Tools binary and execute very fast
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Ocelot Object Database
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Pathway Tools Implementation Details
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Platforms:
 Macintosh, PC/Linux, and PC/Windows platforms
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Same binary can run as desktop app or Web server
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Production-quality software
 Version control
 Two regular releases per year
 Extensive quality assurance
 Extensive documentation
 Auto-patch
 Automatic DB-upgrade

600,000 lines of Lisp code
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Pathway Tools Architecture
Web
Mode
Lisp
Perl
Java
Disk
File
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Pathway
Genome
Navigator
GFP API
Ocelot DBMS
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Desktop
Mode
Protein Editor
Pathway Editor
Reaction Editor
Oracle
or
MySQL
Ocelot Object Database
 Frame
data model
 Classes, instances, inheritance
 Frames have slots that define their properties, attributes,
relationships
 A slot has one or more values

Datatypes include numbers, strings, etc.
 Slotunit
frames define metadata about slots:
 Domain, range, inverse
 Collection type, number of values, value constraints
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Storage System Architecture
 File
KBs
 Read-only
applications can be distributed without
a relational DBMS
 Load all objects and code into Lisp memory
 Dump virtual memory to binary executable file
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Ocelot Storage System Architecture

Persistent storage via disk files, MySQL or Oracle DBMS
 Concurrent development: MySQL or Oracle
 Single-user development: disk files
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Relational DBMS storage
 RDBMS is submerged within Ocelot, invisible to users
 Frames transferred from RDBMS to Ocelot
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On demand
By background prefetcher
Memory cache
Persistent disk cache to speed performance via Internet
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Transaction Logging
 Relational
DBMS stores
 The latest version of each Ocelot frame
 A log of all GFP operations applied to KB
 Transaction
log enables:
 Reconstruction of earlier versions of KB
 View history of changes to an object
 Update replicates of a KB
 Detection of update conflicts during concurrency control
 Undo of updates
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Optimistic Concurrency Control
 Locking
approach: edits to one object can require
locking all connected objects
 No locking
 User
performs updates in local workspace
 When
user commits changes, storage system
compares user changes against all other
committed changes
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Ocelot Knowledge Server
Schema Evolution
 FRSs
store and process class and instance
information similarly
 Application can query schema information as
easily as it can query instances
 Schema
is stored within the DB
 Schema is self documenting
 Schema evolution facilitated by
 Easy addition/removal of slots, or alteration of slot datatypes
 Flexible data formats that do not require dumping/reloading
of data
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Generic Frame Protocol (GFP)
A
library of procedures for accessing Ocelot DBs
 GFP
specification:
 http://www.ai.sri.com/~gfp/spec/paper/paper.html
A
small number of GFP functions are sufficient
for most complex queries
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Example of a Single GFP Call
The General Pattern:
gfp-function(frame slot value ...)
(gfp-function frame slot value …)

LISP
(get-slot-values 'TRYPSYN-RXN 'LEFT)
==> (INDOLE-3-GLYCEROL-P SER)
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Frame References
 At
the GFP level, every Ocelot frame can be
referred to using either symbol frame name or
frame object
 Most
GFP functions return frame objects
 Importance
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of using fequal for comparisons
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Generic Frame Protocol
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
get-class-all-instances (Class)
 Returns direct and indirect instances of Class

coercible-to-frame-p (Thing)
 Is Thing a frame? Returns True if Thing is the name of a frame, or a frame object;
else False
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Generic Frame Protocol

Notation Frame.Slot means a specified slot of a specified
frame. Note: Slot must be a symbol!

get-slot-value(Frame Slot)
 Returns first value of Frame.Slot
get-slot-values(Frame Slot)
 Returns all values of Frame.Slot as a list
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slot-has-value-p(Frame Slot)
 Returns True if Frame.Slot has at least one value; else False
member-slot-value-p(Frame Slot Value)
 Returns True if Value is one of the values of Frame.Slot; else False
Instance-all-instance-of-p(Instance Class)
 Returns True if Instance is an all-instance of Class
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Generic Frame Protocol
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print-frame(Frame)
 Prints the contents of Frame
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Generic Frame Protocol – Update Operations
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
put-slot-value(Frame Slot Value)
 Replace the current value(s) of Frame.Slot with Value
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put-slot-values(Frame Slot Value-List)
 Replace the current value(s) of Frame.Slot with Value-List, which must be a list of
values
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add-slot-value(Frame Slot Value)
 Add Value to the current value(s) of Frame.Slot, if any

remove-slot-value(Frame Slot Value)
 Remove Value from the current value(s) of Frame.slot
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replace-slot-value(Frame Slot Old-Value New-Value)
 In Frame.Slot, replace Old-Value with New-Value
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remove-local-slot-values(Frame Slot)
 Remove all of the values of Frame.Slot
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Generic Frame Protocol –
Update Operations
 save-kb
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Saves the current KB
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Additional Pathway Tools Functions –
Semantic Inference Layer
 Semantic
inference layer defines built-in
functions to compute commonly required
relationships in a PGDB
 http://bioinformatics.ai.sri.com/ptools/ptoolsfns.html
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PerlCyc and JavaCyc
 Work
on Unix (Solaris or Linux) only
 Start up Pathway Tools with the –api arg
 Pathway Tools listens on a Unix socket – perl
program communicates through this socket
 Supports both querying and editing PGDBs
 Must run perl or java program on the same
machine that runs Pathway Tools
 This is a security measure, as the API server has no built-in
security
 Can only handle one connection at a time
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Obtaining PerlCyc and JavaCyc
Download from
http://www.sgn.cornell.edu/downloads/
PerlCyc written and maintained by Lukas Mueller at
Boyce Thompson Institute for Plant Research.
JavaCyc written by Thomas Yan at Carnegie
Institute, maintained by Lukas Mueller.
Easy to extend…
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Examples of PerlCyc, JavaCyc
Functions
GFP
functions (require knowledge of Pathway Tools
schema):
 getSlotValues
 get_slot_values
 getClassAllInstances
 get_class_all_instances
 putSlotValues
 put_slot_values
Pathway Tools functions (described at
http://bioinformatics.ai.sri.com/ptools/ptools-fns.html):
 genes_of_reaction
 genesOfReaction
 find_indexed_frame
 findIndexedFrame
 pathways_of_gene
 pathwaysOfGene
 transport_p
 transportP
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Writing a PerlCyc or JavaCyc program

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Create a PerlCyc, JavaCyc object:
perlcyc -> new (“ORGID”)
new Javacyc (“ORGID”)
Call PerlCyc, JavaCyc functions on this object:
my $cyc = perlcyc -> new (“ECOLI”);
my @pathways = $cyc -> all_pathways ();
Javacyc cyc = new Javacyc(“ECOLI”);
ArrayList pathways = cyc.allPathways ();
Functions return object IDs, not objects.
 Must connect to server again to retrieve attributes of an object.
foreach my $p (@pathways) {
print $cyc -> get_slot_value ($p, “COMMON-NAME”);}
for (int i=0; I < pathways.size(); i++) {
String pwy = (String) pathways.get(i);
System.out.println (cyc.getSlotValue (pwy, “COMMON-NAME”); }
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Sample PerlCyc Query
 Number
of proteins in E. coli
use perlcyc;
my $cyc = perlcyc -> new (“ECOLI”);
my @proteins = $cyc->
get_class_all_instances("|Proteins|");
my $protein_count = scalar(@proteins);
print "Protein count: $protein_count.\n";
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Sample PerlCyc Query
 Print
IDs of all proteins with molecular weight
between 10 and 20 kD and pI between 4 and 5.
use perlcyc;
my $cyc = perlcyc -> new (“ECOLI”);
foreach my $p ($cyc->get_class_all_instances("|Proteins|")) {
my $mw = $cyc->get_slot_value($p, "molecular-weight-kd");
my $pI = $cyc->get_slot_value($p, "pi");
if ($mw <= 20 && $mw >= 10 && $pI <= 5 && $pI >= 4) {
print "$p\n";
}
}
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Sample PerlCyc Query
 List
all the transcription factors in E. coli, and the
list of genes that each regulates:
use perlcyc;
my $cyc = perlcyc -> new (“ECOLI”);
foreach my $p ($cyc->get_class_all_instances("|Proteins|")) {
if ($cyc->transcription_factor_p($p)) {
my $name = $cyc->get_slot_value($p, "common-name");
my %genes = ();
foreach my $tu ($cyc->regulon_of_protein($p)) {
foreach my $g ($cyc->transcription_unit_genes($tu)) {
$genes{$g} = $cyc->get_slot_value($g, "common-name");
}
}
print "\n\n$name: ";
print join " ", values %genes;
}
}
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Sample Editing Using PerlCyc
 Add
a link from each gene to the corresponding
object in MY-DB (assume ID is same in both
cases)
use perlcyc;
my $cyc = perlcyc -> new (“HPY”);
my @genes = $cyc->get_class_all_instances (“|Genes|”);
foreach my $g (@genes) {
$cyc->add_slot_value ($g, “DBLINKS”, “(MY-DB \”$g\”)”);
}
$cyc->save_kb();
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Sample JavaCyc Query:
Enzymes for which ATP is a regulator
import java.util.*;
public class JavacycSample {
public static void main(String[] args) {
Javacyc cyc = new Javacyc("ECOLI");
ArrayList regframes =
cyc.getClassAllInstances("|Regulation-of-Enzyme-Activity|");
for (int i = 0; i < regframes.size(); i++) {
String reg = (String)regframes.get(i);
boolean bool = cyc.memberSlotValueP(reg, “Regulator", "ATP");
if (bool) {
String enzrxn = cyc.getSlotValue (reg, “Regulated-Entity”);
String enzyme = cyc.getSlotValue (enzrxn, “Enzyme”);
System.out.println(enz); } } } }
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Simple Lisp Query Example:
Enzymes for which ATP is a regulator
(defun atp-inhibits ()
(loop for x in (get-class-all-instances '|Regulation-of-Enzyme-Activity|)
;; Does the Regulator slot contain the compound ATP, and the mode
;; of regulation is negative (inhibition)?
when (and (member-slot-value-p x ‘Regulator 'ATP)
(member-slot-value-p x ‘Mode “-”) )
;; Whenever the test is positive, we collect the value of the slot Enzyme
;; of the Regulated-Entity of the regulatory interaction frame.
;; The collected values are returned as a list, once the loop terminates.
collect (get-slot-value (get-slot-value x ‘Regulated-Entity) ‘Enzyme) )
)
;;; invoking the query:
(select-organism :org-id 'ECOLI)
(atp-inhibits)
(get-slot-values 'TRYPSYN-RXN 'LEFT)
==> (INDOLE-3-GLYCEROL-P SER)
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Simple Perl Query Example:
Enzymes for which ATP is a regulator
use perlcyc;
my $cyc = perlcyc -> new("ECOLI");
my @regs = $cyc -> get_class_all_instances("|Regulation-of-EnzymeActivity|");
## We check every instance of the class
foreach my $reg (@regs) {
## We test for whether the INHIBITORS-ALL
## slot contains the compound frame ATP
my $bool1 = $cyc -> member_slot_value_p($reg, “Regulator", "Atp");
my $bool2 = $cyc -> member_slot_value_p($reg, “Mode", “-");
if ($bool1 && $bool2) {
## Whenever the test is positive, we collect the value of the slot
ENZYME .
## The results are printed in the terminal.
my $enzrxn = $cyc -> get_slot_value($reg, “Regulated-Entity");
my $enz = $cyc -> get_slot_value($enzrxn, "Enzyme");
print STDOUT "$enz\n";
}
}
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Getting started with Lisp
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pathway-tools –lisp
(load “file”) (compile-file “file.lisp”)
Emacs is a useful editor
Pathway Tools source code is available: ask
Overview of Lisp information resources:
 http://bioinformatics.ai.sri.com/ptools/ptools-resources.html
Documented Pathway Tools Lisp functions:
 http://brg.ai.sri.com/ptools/ptools-fns.html
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Viewing Results via the Answer List
 (loop
for r in (get-class-all-instances '|Reactions|)
when (< 3 (length (get-slot-values r 'left)))
collect r)
 (setq
answer *)
 (object-table answer)
 (replace-answer-list answer)
 (pt)
 Next
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Answer
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Query Gotchas
 Study
schema carefully
 :test #’fequal
 Cascade of slot-values: check for NIL
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Semantic Inference Layer
relationships.lisp
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Library of functions that encapsulate common query
building blocks and intricacies of navigating the schema
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enzymes-of-gene
reactions-of-gene
pathways-of-gene
genes-of-pathway
pathway-hole-p
reactions-of-compound
top-containers(protein)
all-rxns(type) (:metab-smm :metab-all :metab-pathways :enzyme :transport
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etc.)
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(all-rxns :metab-pathways)
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Pathway Tools Schema and
Semantic Inference Layer
Genes, Operons, and Replicons
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Representing a Genome
components
genome
ORG
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Gene1
CHROM1
Gene2
CHROM2
Gene3
PLASMID1

product
Classes:
 ORG is of class Organisms
 CHROM1 is of class Chromosomes
 PLASMID1 is of class Plasmids
 Gene1 is of class Genes
 Product1 is of class Polypeptides or RNA
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Product1
Polynucleotides
Review slots of COLI and of COLI-K12
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Genetic-Elements
 Sequence
is stored in a separate file or database
table
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Polymer-Segments
Review slots of Genes
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Complexities of Gene / Gene-Product
Relationships
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The Product of a gene can be an instance of Polypeptides
or RNAs
An instance of Polypeptides can have more than one gene
encoding it
Sequence position:
 Nucleotide positions of starting and ending codons specified in Left-EndPosition and Right-End-Position (usually greater, except at origin)
 Transcription-Direction + / Alternative splicing:
 Nucleotide positions of starting and ending codons specified in Left-EndPosition and Right-End-Position
 Intron positions specified in Splice-Form-Introns of gene product
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(200 300) (350 400)
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Gene Reaction Schematic
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Exercises
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
Find all genes on a given chromosome
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Find all ribosomal RNAs
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Find the DNA sequence of a given gene
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Find all proteins longer than 1,000 amino acids
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Exercises
Find all genes on a given chromosome
(defun genes-of-chrom (chrom)
(loop for x in (get-slot-values chrom ‘components)
when (instance-all-instance-of-p x ‘|Genes|)
collect x)
)
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Find all ribosomal RNAs
 (get-class-all-instances ‘|rRNAs|)
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Find the DNA sequence of a given gene
 (get-gene-sequence gene)
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Exercises
 Find
all monomers longer than 1,000 nucleotides
 (loop for g in (get-class-all-instances ‘|Genes|)
for p = (get-slot-value g ‘product)
when (and (< 1000 (abs (- (get-slot-value g ‘left-end-position)
(get-slot-value g ‘right-end-position) )))
(instance-all-instance-of-p p ‘|Polypeptides|) )
collect p )
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Proteins
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Proteins and Protein Complexes
 Polypeptide:
the monomer protein product of a
gene (may have multiple isoforms, as indicated at
gene level)
 Protein
complex: proteins consisting of multiple
polypeptides or protein complexes
 Example:
DNA pol III
 DnaE is a polypeptide
 pol III core is DnaE and two other polypeptides
 pol III holoenzymes is several protein complexes combined
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Protein Complex Relationships
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Slots of a protein (DnaE)
 catalyzes
 Is
it an activator/reactant/etc?
 comments
 component-of
 dblinks
 features (edited in feature editor)
 Many
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other features possible
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A complex at the frame level (pol III)
 Same
features as polypeptide frame, different use
 comment
 component-of
and components
 note coefficients
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Protein Complex Relationships
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Relationships are Defined in Many
Places
 component-of
comes from creating a complex
 appears-in-left-side-of
comes from defining a
reaction (as do modified forms)
 inhibitor-of
comes from an enzymatic reaction
 can
only edit dna-footprint if protein has been
associated with a TU
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Semantic Inference Layer
 Reactions-of-protein
(prot)
 Returns a list of rxns this protein catalyzes
 Transcription-units-of-proteins(prot)
 Returns a list of TU’s activated/inhibited by the given protein
 Transporter? (prot)
 Is this protein a transporter?
 Polypeptide-or-homomultimer?(prot)
 Transcription-factor? (prot)
 Obtain-protein-stats
 Returns 5 values

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Length of : all-polypeptides, complexes, transporters, enzymes, etc…
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Example
 Find
all enzymes that use pyridoxal phosphate as
a cofactor or prosthetic group

(loop for protein in (get-class-all-instances ‘|Proteins|)
for enzrxn = (get-slot-value protein ‘enzymatic-reaction)
when (and enzrxn
(or (member-slot-value-p enzrxn ‘cofactors ‘pyridoxal_phosphate)
(member-slot-value-p enzrxn ‘prosthetic-groups
‘pyridoxal_phosphate))
collect protein)
(member-slot-value-p frame slot value) : T if Value is one of the values of
Slot of Frame.
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Example Queries
 Find
all homomultimers
 Find
proteins whose pI > 10, and that reside on
the negative strand of the first chromosome
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Sample
 Find
all proteins without
a comment anywhere
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Compounds / Reactions / Pathways
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Compounds / Reactions / Pathways
 Think
of a three tiered structure:
 Reactions built on top of compounds
 Pathways built on top of reactions
 Metabolic network defined by reactions alone;
pathways are an additional “optional” structure
 Some reactions not part of a pathway
 Some reactions have no attached enzyme
 Some enzymes have no attached gene
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Compounds
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Compounds
 Relatively
few aspects of a compound defined
within the compound editor
 MW, formula calculated from edited structure
 Most
aspects defined in other editors
 “Pathway reactions” comes from reaction editing followed by
pathway editing
 Activator, etc come from the enzymatic reaction editor
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-- Instance TRP --Types: |Amino-Acid|, |Aromatic-Amino-Acids|, |Non-polar-amino-acids|
APPEARS-IN-LEFT-SIDE-OF: RXN0-287, TRANS-RXN-76, TRYPTOPHAN-RXN,
TRYPTOPHAN--TRNA-LIGASE-RXN
APPEARS-IN-RIGHT-SIDE-OF: RXN0-2382, RXN0-301, TRANS-RXN-76, TRYPSYN-RXN
CHEMICAL-FORMULA: (C 11), (H 12), (N 2), (O 2)
COMMON-NAME: "L-tryptophan"
DBLINKS: (LIGAND-CPD "C00078" NIL |kaipa| 3311532640 NIL NIL),
(CAS "6912-86-3"), (CAS "73-22-3")
NAMES: "L-tryptophan", "W", "tryptacin", "trofan", "trp", "tryptophan",
"2-amino-3-indolylpropanic acid"
SMILES: "c1(c(CC(N)C(=O)O)c2(c([nH]1)cccc2))"
SYNONYMS: "W", "tryptacin", "trofan", "trp", "tryptophan",
"2-amino-3-indolylpropanic acid"
____________________________________________
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Where is diphosphate in the
ontology?
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Semantic Inference Layer
 Reactions-of-compound
(cpd)
 Pathways-of-compound (cpd)
 Is-substrate-an-autocatalytic-enzyme-p (cpd)
 Activated/inhibited-by? (cpds slots)
 Returns a list of enzrxns for which a cpd in cpds is a
modulator (example slots: activators-all, activators-allosteric)
 All-substrates (rxns)
 All unique substrates specified in the given rxns
 Has-structure-p (cpd)
 Obtain-cpd-stats
 Returns two values:

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Length of :all-cpds, cpds with structures
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Miscellaneous things….
History
List
 Back/Forward and History buttons
 Default list is 50 items
 Show
frame
 (print-frame ‘frame)
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Queries with Multiple Answers

Navigator queries:
 Example: Substring search for “pyruvate”
 Selected list is placed on the Answer list
 Use “Next Answer” button to view each one of them

Lisp queries:
Example : Find reactions involving pyruvate as a substrate

(get-class-all-instances ‘|Compounds|)
(loop
for rxn in (get-class-all-instances ‘|Reactions|)
when (member ‘pyruvate (get-slot-values rxn ‘substrates)
collect rxn)
(replace-answer-list * )
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