Genomic approaches enhance phytosanitary research and regulation: using genomics to protect our forests from gypsy moths Gwylim Blackburn, Natural Resources Canada, Canadian Forest Service, Victoria, BC [email protected] Messages

• Biological Invasion (BI): - Widespread, expanding, and costly - Phytosanitary research and regulation is aimed at limiting its impact * • Genomics: - Accessible for any species and ready for widespread uptake - Can enhance our understanding of the entire process of BI, strengthening phytosanitary research and regulation**

* Meghan Noseworthy, Dec 05 2018, CIF Lecture series: “Phytosanitary research and collaboration: Contributing to safe trade of forest products globally” * * Michel Cusson, Feb 13 2019, CIF Lecture series: “Genomic tools to prevent accidental introductions of forest invasive alien species: The case of the Asian gypsy moth” Global extent of biological invasion: widespread, expanding

• Biological invasion: The transportation, introduction, establishment, and spread of a species in a novel environment.

ALL SPECIES

PLANTS INSECTS BIRDS FUNGI MAMMALS

Seebens et al. 2017, Nature Global extent of biological invasion: widespread, expanding

Drivers • global trade, migration

Ricciardi et al. 2017, Trends Ecol & Evol

Rodrigue 2017, “The Geography of Transport Systems” Global extent of biological invasion: widespread, expanding

Drivers • global trade, migration • climate change

NASA (2015)

International Panel on Climage Change (2007) Global costs of insect invasions ... “massive yet grossly underestimated” ...

termite

gypsy moth

Bradshaw et al. 2016, Nature Managing biological invasion: tiers of prevention and response

prevention containment, eradication mitigation

Bradshaw et al. 2016, Nature Phytosanitary research and regulation: global framework

FAO (Food and Agriculture Organization [United Nations])

CPM (Commission on Phytosanitary Measures)

IPPC (International Plant Protection Convention)

NPPO NPPO NPPO (National Plant Protection Organization) NPPO NPPO NPPO (International Standards for NPPO ISPM’s NPPO Phytosanitary Measures)

NPPO 1. “... principles for the protection of plants ...” . . 15. “Regulation of wood packaging ...” NPPO . . 39. “International movement of wood” . • “phytosanitation”: concerning the health of plants . • 183/195 (94%) of all countries belong to the IPPC 42. “Requirements for the use of temperature treatments ...” • Each NPPO must 1. enforce ISPM’s → regulate, certify 2. help develop ISPM’s → research Phytosanitary research and regulation: Pacific Forestry Centre phytosanitary research group FAO (Food and Agriculture Organization [United Nations])

CPM (Commission on Phytosanitary Measures)

IPPC (International Plant Protection Convention)

NPPO

PFC (CFS, NRCan) phytosanitary research group

Eric Leland Meghan Brian Isabel Simon Jun-Jun Joey Gwylim Allen Humble Noseworthy Van Hezewijk Leal Shamoun Liu Tanney Blackburn Managing biological invasions: reconciling research fields

Zenni et al. 2016, AoB Plants; Blackburn et al. 2011, Trends Ecol & Evol Managing biological invasions: the growing availability of genomic data

“single nucleotide polymorphism” Managing biological invasions: the growing availability of genomic data

Genome: an organism’s complete set of DNA, including all of its genes. Genomics: use of genomic data to understand the process of evolution and the genetic structure and function of the traits involved. advent of next-generation sequencing • Rapidly declining sequencing 8 1 x10 costs 7 1 x10 • Rapidly accruing genomic 1 x106 resources (e.g., genome 1 x105

4 assemblies, gene function data) Cost (US (US $) Cost 1 x10

1 x103 • Rapidly accruing statistical tools

1 x102 and computing resources 2002 2004 2006 2008 2010 2012 2014 2016 2018 Year

→ Genomic data is now accessible to all organisms, within even modest research budgets Managing biological invasions: the growing role of genomic data

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0 2008 2010 2012 2014 2016 Year Roe et al. 2018, J Pest Mgmt Managing biological invasions: the growing role of genomic data

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Estoup and Guillemaud 2010, Mol Ecol Allen and Humble 2002, Can J Plant Pathol

Lawson Handley 2011, BioCont Garnas et al. 2016, Biol Invas Fitzpatrick et al. 2012, Biol Invas

Allen et al. 2017, Biol Invas Kirk et al. 2013, Evol Appl

Meurisse et al. 2018, J Pest Sci Chown et al. 2015, Evol Appl

Cristescu 2015, Mol Ecol

Darling 2015, Biol Invas

Rius et al. 2015, Curr Zool Question Knowledge Tool Genomic tools and Question Knowledge Tool What is it? Phylogenomics Management TTaxonaxon Tree Ø Identification •• WhatResearch is it? sspecies/pecies/ framework for enhanced Period Ø Number of lineages, ttypeype MYA degree of divergence Networks Barcoding

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Lymantria dispar asiatica, Asian gypsy moth Asian gypsy moth research team

Richard Ilga Michel Julien Isabelle Sandrine Chris Gwylim Hamelin, Porth, Cusson, Prunier, Giguère, Picq, Keeling, Blackburn, UBC U. Laval NRCan U. Laval U. Laval NRCan NRCan NRCan Variation in female flight capacity across the range of gypsy moths (Lymantria dispar spp.) flight-incapable flight-capable

European gypsy moth Asian gypsy moth (EGM) (AGM) L. d. dispar L. d. asiatica L. d. japonica Research questions

• What forms are being intercepted at ports? - distinguish AGM eggs from those of other gypsy moth types, despite morphological similarity of eggs across types • What is the origin and travel path of intercepted forms? - identify the source and path of AGM arrival, despite complex trade routes • What is the genetic basis of traits mediate invasion risk? - Clarify the genetic basis of AGM female flight capacity in order to profile intercepted specimens for this trait, despite the difficulty in behaviorally measuring flight capacity Global collection flight-incapable flight-capable

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β • Ignores heterozygotic genotypes (i.e., ignores variable loci of U. Laval U. Laval potentially small or compensatory effects on flight, or loci featuring imbalanced dominance) Inbred line breeding design “Rm” ♀ “Ct” ♂ × P

NF F1

NF NN NF FF F2

NF NN NF FF F5 3. Gene expression during pupal development

flight-incapable flight-capable

Rm (30)

Ct (40)

Gene expression Pupal age​ Rm Ct

* 1​ 3​ 3​ 3​ 3​ 3​

*

Relative expression Relative 5​ 3​ 3​

β

β

β 8​ 3​ 3​ β β β

β β

β β 11​ 3​ 3​ 3. Gene expression during pupal development

flight-incapable flight-capable

Rm (30)

Ct (40)

Gene expression ADVANTAGES • Whole-genome, direct comparison of crucial period for flight- * related development between strains LIMITATIONS • * Capturing all expression differences (not necessarily flight-

Relative expression Relative related) during period assayed Michel Chris

β

β •

β Capturing expression only of developmental differences during Cusson, Keeling, β β β

β β

β β larval stages, not adult flight performance or flight-related NRCan NRCan development following maturation • Represents only two locations across geographic range Gene expression results

Factor​ Up Down​ Total​ STRAIN STRAIN × DAY Day​ 3995​ 4706​ 8701​ Strain 357​ 492​ 849​ Strain x Day​ 92​ 78​ 170​

Top 50 outliers from each model term → Candidate genes: individual counts

WITHIN APPROACHES ACROSS APPROACHES

Outliers (all/annotated) Diffl. Pupal gene Approach Seg’n. p < 0.05 q < 0.05 expression GWAS (flight strength) -- 199/89 -- Inbred GWAS (wing length) -- 250/125 -- GWASGWAS lines Inbred lines 139/38 -- -- Pupal gene expr. (strain) -- -- 849/276 Pupal gene expr. (strain X day) -- -- 170/56

• GWAS and inbred line candidate genes: those showing > 0.90 LD with statistical outlier loci. • Outlier status: q < 0.05 (Pupal gene expression); p < 0.05 (GWAS); homozygous genotype (Inbred lines). Candidate genes: individual functional significance

Gene name Biological Process (GO) Analysis Protein tipE male courtship behavior, veined GWAS wing generated song production Protein limb expression 1 homolog imaginal disc-derived wing GWAS morphogenesis Homeobox protein cut imaginal disc-derived wing margin GWAS morphogenesis Heat shock protein 68 embryonic organ development PupExp Putative OPA3-like protein locomotory behavior PupExp Esterase E4 locomotory exploration behavior PupExp Irregular chiasm C-roughest protein nervous system development InbLine Irregular chiasm C-roughest protein brain development GWAS, InbLine, PupExp

• Functional database searches for flight candidate genes. (Shown: selected examples from among ~100 promising candidates) Candidate genes: collective functional significance

regulation of ATPase-coupled calcium transmembrane transporter activity entry into host cell negative regulation of ATPase-coupled positive regulation of ATPase-coupled random inactivation of X chromosome calcium transmembrane transporter calcium transmembrane transporter activity activity viral entry into host cell

negative regulation of calcium ion regulation of calcium ion transport transmembrane transport entry into cell of other organism involved in symbiotic interaction regulation of calcium ion entry into host regulation of calcium ion transmembrane transport transmembrane transporter activity dosage compensation by inactivation of positive regulation of calcium ion negative regulation of calcium ion X chromosome positive regulation of calcium ion transport transmembrane transporter activity positive regulation of calcium ion transmembrane transport negative regulation of calcium ion negative regulationtransmembrane of cation transporter activity viral life cycle transport transmembrane transport regulation of metal ion transport modulation by host of viral genome replication positive regulation by host of viral genome replication

regulation of t-SNARE clustering positive regulation of viral genome regulation of cation transmembrane positive regulation of ion replication entry into other organism involved in positive regulation of clathrin-dependent transport transmembrane transport symbiotic interaction negative regulation of ionregulation of ion transmembrane endocytosis modulation by host of viral process regulation of viral genome replication transmembrane transport positive regulation of cation positive regulation of ion transport transport positive regulation of T cell mediated transmembrane transport cytotoxicity regulation of ion transmembrane positive regulation of t-SNARE clustering regulation of synaptic vesicle clustering regulation of protein localization to dosage compensation negative regulation of ion transporter activity regulation of ion transport negative regulation of ion transport membrane positive regulationpositive of lymphocyte regulation of synaptic vesicle transmembrane transporter activity regulation of clathrin-dependent positive regulation of ion clustering positive regulation by host of viral positive regulation of transmembrane mediated immunity transmembrane transporter activity endocytosis process regulationtransport of T cell mediated cytotoxicity viral process positive regulation of double-strand break repair via nonhomologous end regulation of synaptic vesicle recycling positive regulation of receptor-mediated positive regulation of viral regulationlife cycle of histone H3-K9 methylation joining positive regulation of T cell mediated negative regulation of transmembrane endocytosis positive regulation of protein localization positive regulation of proteasomal immunity transport regulation of transmembrane transport positive regulation of leukocyte to membrane ubiquitin-dependent protein catabolic positive regulation of intracellular regulation of double-strand break repair negative regulation of synaptic vesiclemediated cytotoxicity process negative regulation of histone H3-K9 transport methylation via nonhomologous end joining recycling regulation of lymphocyte mediated • regulation of viral life cycle positiveimmunity regulation of B cell mediatedpositive regulation of phagocytosis “Gene set enrichment” analyses to regulation of transmembrane transporter modification by host of symbiont immunity activity regulation of cellular protein localization morphology or physiology regulation of leukocyte mediated positive regulation of glucose metabolic regulation of histone H4 acetylation positive regulation of cation channel positive regulation of leukocyteregulation of T regulationcell mediated of synaptic immunity vesicle cycle regulation of proteasomal positive regulation of proteasomal cytotoxicity regulation of receptor-mediated regulation of protein targeting activity mediated immunity regulation of intracellular transport ubiquitin-dependent protein catabolic protein catabolic process process positiveendocytosis regulation of intracellularregulation protein of intracellular protein regulation of steroid metabolic process positive regulation of mRNA splicing, via regulation of establishment of protein processregulation of sterol biosynthetic process transport transport positive regulation of mRNA metabolicspliceosome regulation of cation channel activity localization to mitochondrion positive regulation of positive regulation of histone methylation positive regulation of production of positive regulation of transport positive regulation of double-strand regulation of protein localization to ubiquitin-dependent protein catabolic process regulation of histone methylation positive regulationmolecular mediatorof ruffle assembly of immunepositive response regulation of immunoglobulin break repair regulation of cell-matrix adhesion process mediated immune responseregulation of B cell mediatedsynapse immunity modification of morphology or positive regulation of cellular proteinpositive regulation of establishment of positive regulation of carbohydrate regulation of cellular localization positive regulation of immunoglobulin protein localization to mitochondrionpositive regulation of protein targeting to regulation of mRNA splicing, via physiology of other organism involved in regulation of gene silencing by miRNA localization regulation of steroid biosynthetic process regulation of glucoseregulation metabolic of carbohydrate process metabolic metabolic process negative regulation of histone production regulation of establishment of protein mitochondrion symbiotic interactionregulation of double-strand break repair negative regulation of transport regulation of proteasomal protein regulation of cholesterol metabolic process spliceosomemethylationregulation of gene expression, regulation of cell-substrateregulation adhesion of leukocyte regulationmediatedpositive of transport regulation ofregulation adaptive ofimmune phagocytosis localization positive regulation of small molecule positive regulation of protein transport regulation of cholesterol biosynthetic process epigenetic immunity response based on somatic regulation of protein targeting to catabolic process metabolic process positive regulation of histone acetylation positive regulation of transporter activity regulation of protein localization process regulation of mRNA metabolic process negative regulation of transporter activity regulation of ruffle assembly recombination of immune receptorspositive builtregulation of endocytosis mitochondrion regulation of ubiquitin-dependent protein interaction with host positive regulation of gene silencing by positive regulation of cell killingregulation of immunoglobulinfrom immunoglobulinmediated superfamily catabolic process regulation of lipid metabolic process positive regulation of cellular positive regulation of viral process miRNA positive regulation of lipid metabolic regulation of histone acetylation immune response domains carbohydrate metabolicpositive regulationprocess of mRNA processing regulation of productionregulation of molecular of immunoglobulin production process regulation of focal adhesion assemblyregulation of peptide transport positive regulation of proteolysis positive regulation of catabolic process positive regulation of RNA splicing mediatorpositive of immuneregulation response of filopodium positive regulation of establishment of regulation of proteinpositive transport regulation of extracellular matrix involved in cellular protein catabolic positive regulationpositive of lipid regulation biosynthetic of protein catabolic positive regulation of RNA metabolic positive regulation of peptidyl-lysine positive regulation of DNA recombination positive regulation of protein localization positive regulation of chromatin assembly positive regulation of B cell activation disassembly process process process process acetylation symbiont process to synapse protein localization regulation of gene silencing by RNA organization positive regulation of plasma membrane regulation of adaptive immune response regulation of cell killing bounded cellpositive projection regulation assembly of immune effectorbased on somatic recombination of positive regulation of mitochondrion regulation of small moleculeregulation metabolic of cellular carbohydrate regulation of viralregulation process of mRNA processing regulation of cell-substrate junction regulation of glutamine family aminoregulation of alcohol biosynthetic positive regulation of histoneregulation of transporter activity regulation of posttranscriptional gene process regulation of fatty acid metabolic process processpositive regulationmetabolic of fatty process acid immune receptors built from assembly organization iron ion homeostasis regulation of proline metabolic process acid metabolic process process positive regulation of positive regulation of DNAmodification metabolic silencing positive regulation of chromosomeimmunoglobulin superfamily domains metabolicpositive process regulation of cellular catabolic interaction with symbiont process regulation of endocytosis positive regulation of cellular protein nucleobase-containing compound negative regulation of chromatin regulation of plasmapositive membrane regulation of isotype switchingorganization positive regulation of secretion determine if groups of outlier genes regulation of lipid biosynthetic process processpositive regulation by virus of viral positive regulation of NF-kappaB metabolicregulation process of RNA splicing regulation of DNAregulation recombination of chromatin organization positive regulation of lymphocyte positive regulation catabolicof fatty acid process positive regulation of triglycerideprotein levels in host cell transcription factor activity organization bounded cell projection assembly regulation of B cell activation regulation of proteolysis involved in regulation of primary metabolic process positive regulation of metabolic process positive regulation of DNA repair negative regulation of chromosome activation positive regulation of extracellular matrix regulation of extracellular matrix biosynthetic process metabolic process regulation of DNA catabolic process modification of morphology or positive regulation of protein secretion disassembly cellular protein catabolic process positive regulation of triglyceride positive regulation ofregulation posttranscriptional of filopodium assemblyorganization regulation of vesicle-mediated transport organization regulation of catabolic process regulation of peptidyl-lysinephysiology acetylation of other organism regulation of localization biosynthetic processpositive regulation of biosynthetic regulation of histone modification regulation of cell adhesion regulation of mitochondrion organization negative regulation of endoplasmic regulation of RNApositive metabolic regulation process of macromolecule gene silencing positive regulation of cell projection negative regulation of proline metabolic regulation of cellular amino acid positive regulationprocess of protein metabolic regulation of terminalregulation button of organization AMPA receptor activity regulation of isotype switching reticulum calcium ion concentration regulation of protein catabolicregulation process of triglyceride metabolic metabolic process regulation of DNA repair organization regulation of proline biosyntheticprocess process metabolic process processpositive regulation of RNA biosynthetic positive regulation of dendrite regulation of secretion process positive regulation of protein acetylation positive regulationregulation of AMPA of receptor plasma membrane regulation of chromosome organization regulation of adherens junction positive regulation of peptide secretion process development regulation of NMDA receptor activity regulation of lymphocyte activationregulation of peptide secretion regulation of cellular ketone metabolic boundedactivity cell projection organization organization positive regulationnegative of regulation nitrogen of DNA catabolic regulation of cell projection assembly positive regulation of organelle transition metal ion homeostasis regulation ofregulation fatty acid ofbiosynthetic triglyceride biosyntheticprocess regulation of DNA metabolic process negative regulation of dendrite regulation of immune effector process organization positive regulation of insulin secretion compound metabolic processprocess negative regulation of histone regulation of symbiosis, encompassing positive regulation of neuron projection positive regulation of cellular component process process regulation of cellular catabolic process regulation of dosage compensationmutualism through by parasitism development regulation of cell projection organization regulation of nucleobase-containing modification developmentpositive regulation of axonogenesis positive regulation of reproductive biogenesis positive regulation of cellular metabolic inactivation of X chromosome negative regulation of flagellated sperm positive regulation of basement negative regulation of small molecule compound metabolic process positive regulation of dendritic spine regulation of presynapsepositive assembly regulation of biological process regulation of extracellular matrix positive regulation of DNA regulation of cellular protein catabolic process positive regulation of DNA-binding motility process positive regulation of cellularmembrane component assembly involved in endoplasmic reticulum calcium ion regulation of cellular amino acid positive regulation of cellular developmentnegative regulation of dendritic spine regulationorganization of protein secretionnegative regulation of protein topoisomerase (ATP-hydrolyzing)negative regulation of proline metabolic process positive regulation of gene expression negative regulation of neuron projection regulation of flagellated sperm motility organizationembryonic body morphogenesis homeostasis biosynthetic process process biosynthetic process development transcription factor activity regulation of cell junction assembly positive regulation of microtubule activity biosynthetic process negative regulationpositive regulation of cell projection of developmental positive regulation of behavior depolymerization negative regulation of cellular amino regulation of biosynthetic process positive regulation of macromolecule development negative regulation of axonogenesis positive regulation of leukocyte activation regulation of basement membraneregulation of protein depolymerization nucleation negative regulation of catabolicregulation process of metabolic process positive regulation of molecular function growth biosyntheticregulation process of protein acetylation negative regulation of dendrite organization organization positive regulation of isomerase activityacid metabolic process regulation of protein metabolic process regulation of macromolecule metabolic regulation of neurotransmitter receptor positive regulation of cell negative regulationnegative of inclusion regulation body of organellepositive regulation of protein complex morphogenesisregulation of presynapse organization positive regulationpositive regulation of growth of locomotion regulation of protein complex positive regulation of proteolysis process activity positive regulation of axon extensionmorphogenesis involved in positive regulation of adaptive immuneassembly organization assembly regulation of cellular amine metabolicregulation of RNA biosynthetic process regulationpositive of dendrite regulation development of signalingregulation receptor of gene silencing positive regulation of synapse assembly disassembly regulation of aminoacyl-tRNA ligase negative regulation of molecular function differentiation response regulation of inclusion body assembly regulation of leucine-tRNA ligase activity processpositive regulation of cellular protein activity negative regulation of reproductive negative regulation of protein complex positive regulation of nucleic negative regulation of dendritic spine regulation of locomotion regulation of insulin secretion positive regulation of microtubule calcium ion homeostasis activity metabolic processnegative regulationnegative of regulation cellular catabolic of RNA metabolic regulation of neuron projection process negative regulation of microtubule regulation of DNA topoisomerase acid-templated transcription regulationpositive of reproductive regulation process of developmental disassembly regulation of macrophage activation process process negative regulation of DNA metabolic morphogenesispositivedevelopment regulation of multi-organismnegative regulation of synapse positive regulationpositive of regulation embryonic of secretion by cell depolymerization polymerization (ATP-hydrolyzing) activity regulation of ligase activity positive regulation of catalytic activity regulation of macromolecule process regulation of axonogenesisnegativeorganization regulation of cell process regulation of organelle organization regulation of isomerase activity process positive regulation of immune system development positive regulation of peptide hormone negative regulation of cellular amino regulation of cellular biosyntheticbiosynthetic process regulation of gene expressionregulation of dendritic spine morphogenesis involved in positive regulation of oviposition secretion regulation of microtubule nucleation metal ion homeostasis regulation of cellularpositive metabolic regulationpositive process of regulationcellular amide of protein regulation of dendritic spine process regulation of leukocyteregulation activation of basement membrane positive regulation of ATPase activity acid biosynthetic processregulation of proteolysis regulation processby virus positiveof viral proteinregulation levels of oxidoreductase development regulation of dendrite morphogenesis differentiation positive regulation of supramolecular cellular calcium ion homeostasis positive regulation of phosphorus metabolic process morphogenesis regulation of developmental growth regulation of cellular component regulation of microtubule in host cell activity modificationregulation process of DNA biosynthetic processnegative regulation of DNA-binding positive regulation of cell growth negative regulation of cellular regulation of cellular componentassembly involved in embryonic body fiber organization positive regulation of phosphatase metabolic process regulation of nitrogen compound regulation of cell motility organization depolymerization transcription factor activity negative regulation of axon extension regulation of behaviorcomponent organization biogenesis morphogenesisnegative regulation of supramolecularpositive regulation of cytoskeleton positive regulation of microtubule negative regulation of aminoacyl-tRNA regulation of phosphoprotein negative regulation of regulation of postsynapse organization negative regulation of locomotion from across all analyses exhibit activity metabolic process positive regulation of response to DNA negative regulation of protein complex fiber organizationnegative regulation of cytoskeletonorganization polymerization or depolymerization negative regulation of leucine-tRNA negative regulation of biosynthetic nucleobase-containing compoundpositive regulation of reactive oxygen regulation of synapse assembly positive regulation of cell activation ligase activity phosphatase activity negative regulation of metabolic process positive regulation of neurondamage stimulus regulation of growth assembly regulation of protein complex assembly organization negative regulation of microtubule ligase activity process metabolic process species metabolic process negative regulation of ligase activity negative regulation of cellular amine differentiation negative regulation of cell motility positive regulation of proteinpolymerization or depolymerization divalent inorganic cation homeostasis negative regulation of protein metabolic interspecies interaction between negative regulation of neuron negative regulation of developmental positive regulation of cell motility regulation of microtubule polymerization metabolic processregulation negative of cellular regulation protein of metabolicRNA biosynthetic negative positiveregulation regulation of growth of cell development polymerization positive regulation of hydrolaseregulation activity of protein dephosphorylation regulation of DNA-binding transcription differentiation regulation of cell morphogenesispositivegrowth regulation of nervousregulation system of cellular componentregulation of adaptive immune response positive regulation of dephosphorylation process processnegative regulation of DNA biosynthetic organisms negative regulation of actin filament regulation of catalytic activity process regulation of nucleicpositive acid-templated regulation of transcription, regulation of response to DNA damage regulation of glutamate receptorinvolved in differentiation development movement regulation of supramolecular fiber cellular metal ion homeostasis regulation of oxidoreductase activity factor activity regulation of multi-organism process positive regulation of hemopoiesis regulation of embryonic developmentregulation of peptide hormone secretion bundle assembly processtranscription DNA-templated regulation of immune system process regulation of secretion by cell organization regulation of ATPase activity negative regulation of catalytic activityregulation of phosphorus metabolic negative regulation of macromolecule positive regulation of DNA-templated stimulus signaling pathway positive regulation of multicellular regulation of biologicalpositive process regulation of cell differentiation regulation ofnegative phosphatase regulation activity of phosphoprotein process biosynthetic process transcription, elongation positiveregulation regulation of axon ofextension glutamate receptor organismal process inorganic ion homeostasis regulation of protein modification positive regulation of cellularregulation process of developmental process regulation of organelle assembly cellular divalent inorganic cation phosphatase activity negative regulationregulation of ofcellular reactive oxygenprocess species regulation of cellular amide metabolic signaling pathway regulation of actin filament bundle negative regulation of stress fiber positive regulation of GTPase activity positive regulation of phosphate regulation of cellular macromolecule negative regulation of cellregulation development of synapse organization regulationregulation of oviposition of multicellular organismal homeostasis regulation of calcium-dependent biosynthetic processbiosynthetic process negativeprocess regulation ofregulation macromolecule of molecular function negative regulation of biological process assembly assembly metabolic process negative regulation of cellular metabolic developmentregulation ofregulation cell activation of muscle tissue development regulation of microtubule polymerization cation homeostasis ATPase activity biosynthetic process regulation of muscle organ developmentregulation of striated muscle tissue regulation of protein polymerization positive regulation of dUTP negative regulation of protein process metabolic process regulation of neuron differentiation negative regulation of cellnegative growth regulation of cellular positive regulation of cellular component or depolymerization negative regulationnegative of regulation protein of cellular proteinnegative regulation of nitrogen regulation of defense response to virus regulation of cell growth diphosphatase activityregulation ofregulation hydrolase of activity dephosphorylationdephosphorylation positive regulation of translation regulation of signaling receptor activity regulation of anatomical structure development negative regulation of proteolysismodification process compoundregulation metabolic of reactive process oxygen species positive regulation of cell populationnegative regulationcomponent of developmental movement movement regulation of cytoskeleton organization regulation of cyclic-nucleotide metabolic process positive regulation of transcription positive regulation of cellular response morphogenesis regulation of gastrulation regulation of GTPase activity metabolic process positive regulation of removal of positive regulation of neurogenesisproliferation process positive regulation of cell negativemigration regulation of cell migration phosphodiesterase activity positive regulation of superoxideelongation from RNA polymerase II regulation of modification of synapticto oxidative stress regulation of nervous system positive regulation of peptidase activity superoxideregulation radicals of DNA-templated positive regulation of epithelialpositive cell regulation of hormone secretion dismutase activity promoter structure development regulation of epithelial to mesenchymal positive regulation of Arp2/3 transcription, elongation regulation of stress fiber assembly negative regulation of phosphatase negative regulation of GTPasenegative activity regulation of cellular posttranscriptional regulation of gene regulation of cell development regulation of hemopoiesisregulation of bone developmenttransition migration complex-mediated actin nucleation negative regulation of ATPase activity negative regulation of phosphorus regulation of cell differentiation positive regulation of cytokine production regulation of nuclear division activity negative regulation of reactive oxygenmacromolecule biosynthetic process expression regulation of phosphate metabolic negative regulation of neurogenesis negative regulationpositive of cellregulation differentiation of neuron migration positive regulation of protein folding regulation of Arp2/3 complex-mediated cellular cation homeostasis negative regulation of regulation of dUTP diphosphatase negative regulation of hydrolase activity metabolic processspecies biosynthetic process regulation of cell migration processregulation of peptidase activity negative regulation of nucleic positive regulation of actin nucleation actin nucleation activity negative regulation of dephosphorylation regulation of superoxide dismutase positive regulation of response to negative regulation of morphogenesis of calcium-dependent ATPase activity acid-templated transcription positive regulation of cellular response regulation of post-embryonic positive regulation of interleukin-8positive regulation of actin filament activity positive regulation of transcription by positive regulation of response to stimulus an epithelium regulation of protein modification by regulation of nitric oxide biosynthetic positive regulation of responsenegative to regulation of nervous system positive regulation of myeloid cell to alcohol polymerization regulation of transferase activity RNA polymerase II reactive oxygenregulation species of epithelial cell proliferation development production negative regulation of transferase activity negative regulation of protein process regulation of transcription, oxidativeregulation stress of cell population proliferationdevelopment differentiation positive regulation of protein refolding regulation of spindle assembly regulation of actin nucleation negative regulation of cyclic-nucleotide small protein conjugation or removal regulation of cell morphogenesispositive regulation of signaling regulation of morphogenesis of an regulation of actin filament organization modification by small protein negative regulation of reactive oxygen regulation of response to biotic stimulus phosphodiesterase activity regulation of modificationDNA-templated of negative regulationregulation of cell of population defense response to virus negative regulation of woundepithelium healing, regulation of actin filament conjugation or removal negative regulationspecies of nitricmetabolic oxide process positive regulation of response to regulation of epithelial cell migration regulation of microtubule cytoskeleton ion homeostasis regulation of superoxide metabolic postsynaptic structure proliferation by host regulation of neuron migrationnegative regulation of bone development spreading of epidermal cells polymerization negative regulation of phosphate positive regulation of phosphorylation biosynthetic process regulation of transcriptionnegative elongation regulation of epithelial cell external stimulus organization process regulation of cellular response to regulation of defense response positive regulationpositive ofregulation response of to immune alcohol response regulation of microtubule-based process metabolic process regulation of removalfrom of superoxide RNA polymerase II promoterproliferation positive regulation of defense response functional themes. negative regulation of cellular process regulation of protein folding regulation of binding oxidative stress regulation of responseregulation to external of cellular process positive regulation of cell communication negative regulation of peptidase activity radicals regulation of response to osmotic stress regulation of actomyosin structure stimulus regulation of cellular responseregulation to alcohol of wound healing, spreadingregulation of cytokine production organization positive regulation of protein positive regulation of response to biotic regulation of actin filament-based regulation of interleukin-8 production regulation of protein ubiquitination regulation of cellular response to drug regulation of extent of cell growthregulation of multicellularnegative regulation organismal of proteinof foldingepidermal cells negative regulation of protein phosphorylation regulation of translation stimulus process regulation of protein refolding regulation of response to reactiveregulation of responsenegative to oxidative regulation stress of cellular response regulation of signalingprocess ubiquitination negative regulation of transcription, oxygen species to oxidative stress regulationregulation of innate immuneof myeloidpositive response cell regulation differentiation of innate immune positive regulation of abscisic regulation of phosphorylation DNA-templated negative regulation of kinase activity regulationnegative of neurogenesis regulation of cellular response response acid-activated signaling pathway regulation of photomorphogenesisregulation of actin cytoskeleton regulation of modification of positivenegative regulation regulation of regulationcell of death response of response to to alcohol regulation of protein binding negative regulation of nitric oxide to drug regulation of response to stimulus regulation of hormone secretion organization regulation of spindleregulation organization of mitotic spindle assembly postsynaptic actin cytoskeleton regulation of oxidative stress-induced negative regulation of multicellular wounding positivenegative regulation regulation of neurological of wound healing metabolic process regulation of hydrogen peroxide-induced regulation of establishment or cellular ion homeostasis negative regulation of phosphorylationnegative regulation of protein regulation of transcription by RNA regulation of cellular response to stressregulation of response to stress organismalnegative process regulation of signaling water homeostasis cell deathpositive regulation of defensecell responsedeath regulation of immunesystem response process negative regulation of protein refolding regulation of kinase activity phosphorylation polymerase II regulation ofnegative response regulation to drug of response to maintenance of cell polarity regulation of cellular response to heat to virus by host positive regulation of response to regulation of actin polymerization or regulation of endopeptidase activity stimulus regulation of mitoticregulation nuclear division of centrosome cycle regulation of abscisic acid-activatedregulation of cell communication depolymerization regulation of mitotic centrosome regulation of cellular response tocytokine growth stimulus regulation of response to red or far red positive regulation of cell cycle positive signalingregulation pathway of signal transduction regulation of establishment of cell separation positive regulation of translational regulation of BMP signalingnegative pathway regulation of response to drug factor stimulus light negative regulation of response to positive regulationregulation of erythrocyte of response to wounding polarity regulation of protein heterodimerization negative regulation of transcription by regulationpositive of wound regulation healing of toll-like receptor regulation of protein phosphorylationpositive regulation of endopeptidase initiation negative regulation of response to differentiation activity RNA polymerase II negative regulation of hydrogenoxidative stress positive regulation of nucleotide-binding signaling pathway activity reactive oxygen species oligomerization domain containing negative regulation of cell regulation of toll-like receptor signaling negative regulation of protein kinase chemical homeostasis peroxide-induced cell death negative regulation of oxidative negative regulation of endopeptidase regulation of response to water regulation of cell deathcommunication pathway carbohydrate homeostasis stress-inducedregulation cell death of transmembrane signaling pathway receptor regulation of neurotrophin TRK receptor positive regulation of synaptic activity positiveactivity regulation of peptidyl-serine deprivation regulation of mitotic spindle organization protein serine/threonine kinase signaling signaling pathway positive regulation of excitatorytransmission regulation of cell cycle process lipid homeostasis phosphorylation positive regulation of MAPK cascade regulationpositive of cellregulation cycle of toll-like receptor 2 glucose homeostasis negativepathway regulationregulation of cell of death response to cytokine postsynaptic potential regulation of nucleotide-binding positive regulation of Notch signaling signaling pathway regulation of proteinnegative kinase regulationactivity of protein positive regulation of translation in stimulus positive regulation of cell cycle process positive regulation of intracellular signal pathway positive regulation of smoothened autophosphorylationregulation of protein autophosphorylation response to stress regulation of translation at synapse oligomerization domain containing negative regulation ofregulation response of to trans-synaptic signaling regulation of cell cycle phase transition negative regulation of transcription from transduction regulation of signal transduction positive regulationpositive of neurotrophin regulation TRKof inhibitory regulation of cell cycle G2/M phase signaling pathway external stimulus signalingregulation pathway of toll-like receptor 2 signaling negative regulation of cell cycle arrest RNA polymerase II promoter in regulation of stress-activated protein regulation of fibroblast growth factor receptor signalingpostsynaptic pathway potential transition negative regulation of cAMP-dependent negative regulation of protein regulation of synapse structure or activity negative regulation of neurological pathway response to stress kinase signaling cascade receptor signaling pathway → regulation of peptidyl-serine positive regulation of cytokine-mediatednegative regulation system of synaptic process protein kinase activity serine/threonine kinase activity positive regulation of cell cycle phase potentially exposing the functional phosphorylation negative regulation of gene expression signaling pathway transmission regulation of cell cycle arrest transition cellular glucose homeostasis regulation of MAPKregulation cascade of translational initiation positive regulation of nucleotide-binding regulation of neurological system positive regulation of mitotic cell cycle positive regulation of programmed cell positive regulation of synaptic regulation of transcription from RNA oligomerization domain containing 2 process regulation of mitotic cell cycle death transmission,negative GABAergic regulation of cell cycle process positive regulation of cell cycle G2/M polymerase II promoter in response to signalingregulation pathway of erythrocyte differentiation negative regulation of signalregulation transduction of smoothened signaling regulation of cAMP-dependent proteinregulation of protein serine/threonine positive regulation of peptidyl-serine regulation of receptor signaling pathway regulation of cysteine-type stress cell redox homeostasis regulation of Notch signaling pathway positivepathway regulation of apoptotic signaling phase transition kinase activity kinase activity phosphorylation of STAT protein negative regulation of cysteine-type via STAT modulation of excitatory postsynaptic positive regulation of synaptic regulation of mitotic cell cycle phase regulation ofregulation peptidyl-serine of stress-activated MAPK endopeptidase activity regulation of G negativeprotein-coupled regulation receptor of excitatory pathway regulation of G2/M transition of mitotic endopeptidase activity positive regulation of stress-activated regulation of translation at synapse, modulationpotential of inhibitory postsynaptic transmission, glutamatergic transition cellular chemical homeostasis cascade regulation of intracellularregulation signal of nucleotide-binding regulation of cytokine-mediatedsignaling postsynapticpathway potential cell cycle phosphorylation of STAT protein protein kinase signaling cascade modulating synaptic transmission potential transductionoligomerization domain containing 2 signaling pathway regulation of actin filament length positive regulation of mitotic cell cycle positive regulationregulation of stress-activated of receptor signaling pathway regulation of translation at postsynapse signaling pathway regulation of programmed cell deathactivation of innate immune response phase transition regulation of JNK cascade negative regulation of cell cycle MAPK cascade via JAK-STAT regulation of neurotransmitter levels positive regulationregulation of oftranslational eIF2 alpha phosphorylation regulation of gibberellic acid mediated regulation of synaptic transmission, positive regulation of tumor necrosis modulation of chemical synaptic positive regulation of G2/M transition of initiation in responseby amino to stress acid starvation negative regulation of programmedsignaling pathway cell regulation of ERBB signaling pathway GABAergic biological regulation factor-mediated signaling pathway transmission actinpositive nucleation regulation of extrinsic apoptotic mitotic cell cycle positive regulation of JNK cascade death regulation of apoptotic signaling pathway signaling pathway regulation of p38MAPK cascade regulationregulation of cysteine-typeof translation at postsynapse, negative regulation of gibberellic acid regulation of synaptic transmission, negative regulation of signal positive regulation of cysteine-type modulating synaptic transmissionregulation of cell shape regulation of respiratorymediated gaseous signaling pathway glutamatergic Arp2/3 complex-mediated actin endopeptidase activity involved in transduction in absence of ligand endopeptidase activity exchange positive regulation of apoptotic process nucleation negative regulation of cysteine-typeapoptotic process regulation of cell size positive regulation of p38MAPK cascade endopeptidase activity involved in regulation of system process regulation of small GTPase mediated postsynaptic modulationnegative of chemical regulation of blood circulation negative regulation of ERBB signaling apoptotic process signal transduction synaptic transmission regulation of TOR signalingregulation of tumor necrosis pathway regulation of extrinsic apoptotic regulation of epidermal growth factor regulation of calcium-mediated signaling factor-mediated signaling pathway regulation of apoptotic process signaling pathway regulation of membrane potential negative regulation of apoptoticreceptor signaling pathway regulation of protein kinase A signaling negative regulation of extrinsic apoptotic regulation of translational initiation in signaling pathway signaling pathway in absence of ligand response to stress rhythmicnegative synaptic regulation transmission of mitotic cell cycle regulation of extrinsic apoptotic activation of immune response innate immune response-activating polyamine metabolic process regulation of synaptic plasticity signaling pathway in absence of ligand significance of candidate genes that regulation of translation in response to signal transduction regulation of DNA-templated negative regulation of apoptotic process stress transcription in response to stress negative regulationnegative of epidermal regulation growth of extrinsic apoptotic methylglyoxal catabolic process to factor receptor signalingsignaling pathway pathway D-lactate via S-lactoyl-glutathione positive regulation of translational membrane depolarization regulation of myeloid cell apoptotic calcium ion transport polyamine biosynthetic process diterpenoid metabolic process initiation in response to starvation negative regulation of cell size process regulation of blood circulation retinoid metabolic process protein stabilization regulation of muscle cell apoptotic pattern recognition receptor signaling calcium ion transmembrane transport regulation of biological quality homophilic cell adhesion via plasma regulation of protein complex stability process immune response-activating signal pathway nicotine catabolic process regulation of long-term synaptic membrane adhesion molecules positive regulation of membrane regulation of protein stability negative regulation of myeloid cell transduction permeability potentiation cellular homeostasis apoptotic process cellular biogenic amine catabolic process cellular biogenic amine metabolic positive regulation of lysosomal regulation of buoyancy regulation of hormone levels toll-like receptor signaling pathway divalent metal ion transport negative regulation of muscle cell cell-cell adhesion via plasma-membrane process primary alcohol metabolic process methylglyoxal catabolic processterpenoid to metabolic process membrane permeability regulation of membrane permeability negative regulation of vasoconstriction adhesion molecules apoptotic process lactate inorganic cation transmembrane retinol metabolic process folic acid catabolic process dicarboxylic acid catabolic process sodium ion transport transport G1/S transition of mitotic cell cycle establishment or maintenance of cell nitrate assimilation immune response-regulating signaling nicotine metabolic process polarity regulating cell shape activation of cysteine-type neuron cell-cell adhesion regulation of striated musclepathway cell retinal metaboliccellular biogenicprocess aminetetrahydrofolate biosynthetic metabolic process secondary alcohol metabolic processcholesterol metabolic process divalent inorganic cation transport mitotic cell cycle checkpoint endopeptidase activity regulation of translational initiation regulationin of cellular component size apoptotic process process monovalent inorganic cation transport homeostatic process gene silencing by RNA tryptophan catabolic process to altruistic, chimeric sorocarp development homeostasis of number of cells response to starvation actin filament bundle retrograde indolalkylamine catabolic process coenzyme catabolic process altruistic, chimeric, non-reproductive negative regulation of striated muscle oxidoreduction coenzyme metabolic potassium ion transport gene silencing regulation of respiratory systemadaptation process of signaling pathway transport kynurenine fruiting body development cell apoptotic process folic acid-containing compound process drug catabolic process methylglyoxal catabolic processwater-soluble vitamin catabolic process metal ion transport inorganic ion transmembrane transport catabolic process secondary alcohol biosynthetic process actin filament organization nitrate metabolic process cholesterol biosynthetic process cell cycle G1/S phase transition regulation of lysosomal membrane neurotransmitter metabolic process folic acid metabolic process dicarboxylic acid metabolic process mitotic cell cycle phase transition immune response-activating cell surface cell-cell adhesion ubiquinone metabolic process amine catabolic process individually show only modest or cation transmembrane transport permeability cell cycle checkpoint regulation of vasoconstriction indolalkylamine metabolictryptophan process catabolic process mitotic DNA integrity checkpoint actin filament regulationbundle distribution of cardiac muscle cell receptor signaling pathway tetrahydrofolate interconversion actin filament bundle organization nitrogen cycle metabolic process chimeric sorocarp development cellular response to amino acid apoptotic process carboxylic acid catabolic process cation transport starvation reactive nitrogen species metabolic lactate metabolic processglutamate metabolic process generation of neurons negative regulation of cardiac muscle cellular amine metabolic process cellular modified amino acid catabolic coenzymewater-soluble metabolic vitamin process metabolic process chimeric non-reproductive fruiting body mitotic cytokinesis cellular response to leucine starvation process alcohol metabolic process DNA integrityregulation checkpoint of anatomical structure size cell apoptotic process cell adhesion mediated by integrin cofactor catabolic processprocess development cortical cytoskeleton organization neurotransmitter catabolic process methylglyoxal metabolic process ubiquinone biosynthetic process drug metabolic process alpha-amino acid catabolic process sterol metabolic process myeloidcortical cell homeostasis actin cytoskeleton organization positive regulation of blood vessel Fc receptor mediated stimulatory attachment of mitotic spindle diameter signaling pathway aldehyde catabolic process histidine foliccatabolic acid-containing process compound sorocarp development erythrocyte homeostasis protein tetramerization neutrophil activation acetylcholine metabolic process aromatic amino acid family catabolic metabolic process mitotic actomyosin contractile ring microtubules to kinetochore cellular hormone metabolic process tryptophan metabolic process quinone metabolic process mitotic cytokinetic process pteridine-containing compound catabolicprocess isoprenoid metabolic process assembly cell cycle phase transition mitotic cell cycle process hormone metabolic process acetylcholine catabolic process kynurenine metabolic process granulocyte activation indole-containing compoundprocess catabolic ketone catabolic process vitamin catabolic process imidazole-containingprocess compound ceramide catabolic process quinone biosyntheticsterol process biosynthetic process regulation of nucleosome density mRNA catabolic process ammonium ion metabolic process alcohol biosynthetic process establishment of cell polarity catabolic process cellular amino acid catabolic processceramide metabolic process non-reproductivechimeric fruiting colonial body development actomyosin contractileastral microtubulering organization organizationmulti-organism processmicrotubule polymerization or myeloid leukocyte activation immune response-regulating cell assembly ofactomyosin actomyosin contractile apparatus ring assemblymitotic spindle organization ion transmembrane transport actin cytoskeletonmicrotubule organization polymerization surface receptor signaling pathway amine metabolic process development depolymerization neutrophil activation involved in immune cell adhesion Fc receptor signaling pathway oxoacid metaboliccarnosine processmetabolic process histidine metabolic process water-solubleglutamine vitamin biosynthetic family amino acid metabolic involved in mitotic cytokinesis organic acid catabolic processcofactor metabolic processcarboxylic acid metabolic processvitamin metabolic process fat-soluble vitamin metabolic process proton-transporting V-type ATPase response hormone catabolic process coenzyme biosyntheticprocess process process cytoskeleton-dependent cytokinesis vacuolar proton-transporting V-type Fc-gamma receptor signaling pathway territorial aggressive behavior mitotic metaphase plate congression myeloid cell activation involved in cellular aldehyde metabolic process microtubule cytoskeleton organization complex assembly ATPase complex assembly aromatic amino acid family metabolic erythrocyte differentiation cytoplasmic microtubule organizationmicrotubule nucleation immune response alkaloid metaboliccellular process catabolic process indole-containingpteridine-containing compound metabolic compound organic hydroxy compound metabolic mitotic nuclear division involved in mitosis protein polymerization myeloid leukocyte mediated immunity one-carbon metabolic process process sphingolipid catabolic process L-ascorbic acid metabolic process mitotic spindle elongation organic cyclic compound catabolic processmetabolic process process nitrogen compound metabolic process organonitrogen compound catabolic steroid metabolic process monocarboxylic acid metabolic process intraspecies interaction between lysosome organization establishment or maintenance of cell leukocyte activation involved in immune neutrophil mediatedFc-gamma immunity receptor signaling pathway process imidazole-containingcellular compound ketonebenzene-containing metabolic process compound attachment of spindle microtubules to proton-transporting two-sector ATPaseleukocyte activation nuclear-transcribed mRNA catabolic cellular nitrogen compound catabolic process organisms cytokinetic process polarity response leukocyte mediated immunity aromatic compound catabolic process metabolic process kinetochore complex assembly involved in phagocytosis process nuclear-transcribed mRNA catabolic process metabolic process actomyosin structure organization mitotic spindle assembly cytoskeleton organizationmitotic cellestablishment cycle of mitotic spindle process, non-stop decay amine biosynthetic process alpha-amino acid metabolic process monocarboxylic acid biosynthetic fatty acid elongation zymogen activation acetate ester metabolic processcellular modified amino acid metabolic phosphatidylcholine catabolic process immune system process regulation of blood vessel diameterhormone transport cellular amide metabolic process cofactor biosynthetic process organic hydroxy compound biosynthetic spindle organization localization small molecule catabolic process process very long-chain fatty acid metabolic nuclear division lysosomal membrane organization heterocycle catabolic processprocess process protein complexestablishment oligomerization of spindle orientation neutrophil degranulation mucopolysaccharide metabolic process lipid catabolic process steroid biosynthetic process mitotic sister chromatid segregation supramolecular fiber organization cellular response to glucose starvation sphingolipid metabolic process membrane lipid metabolic process process myotube differentiation myoblast fusion response to virus immune effector process catabolic process organic substance catabolicphosphatidylcholine process metabolic process vitamin biosynthetic process socially cooperative development meiosis I ion transportestablishment or maintenance of L-ascorbic acid biosynthetic process chondroitin sulfate metabolic process organic acid organicmetabolic cyclic process compound metabolic ketone biosynthetic process glycerophospholipid catabolic process obscure connection to female flight aggressive behavior endoplasmic reticulum polarization anatomical structure homeostasis immune response-regulating cell cellular nitrogen compound metabolic assembly of actomyosin apparatus cytoskeleton polarity response to amino acid starvation leukocyte degranulation process pyrimidine nucleotide-sugar surface receptor signaling pathway process fatty acid metabolic process very long-chain fatty acid biosynthetic gliogenesis cell cycle process chondroitin sulfatesecondary proteoglycan metabolic process organonitrogen compound metabolic cellular lipid catabolic process fatty acid biosynthetic process lytic vacuole organization involved in cytokinesiscytokinesis regulation of tube size cellular response to starvation involved in phagocytosis nuclear-transcribed mRNA catabolic heparan sulfate proteoglycan metabolic cellular aromatic compound metabolic carboxylic acid biosynthetic process process microtubule cytoskeleton organization transmembrane transport metabolic process process small molecule metabolic process membrane lipid catabolic process regulation of tube diameter process, no-go decay process process spindle elongation cellular protein-containing complex nucleobase-containing compound in utero embryonic development male meiosis I metaphase plate congression oxidation-reduction process neurogenesis meiotic nuclear division social behavior syncytium formation by plasma heterotrimeric G-protein assemblycomplex late endosomal microautophagy catabolic process melanin metabolic process heterocycle metabolicphenol-containing process compound metabolic lipid metabolic process cellular metabolic process peptide metabolic process organic acid biosynthetic process glycerolipid catabolic process pyruvate metabolic process mitochondrial membrane fission membrane fusion establishment or maintenance of nuclear chromosome segregation assembly cell activation involved in immune cellularprocess amino acid metabolic process oligodendrocyte differentiation spindle assembly cell activation RNA surveillance cellular lipid metabolic process hemopoiesis response small molecule biosynthetic process myeloid cell differentiation microtubule cytoskeleton polarity actin filament-based process regulated exocytosis chondroitin sulfate proteoglycan lipid biosynthetic process biological adhesion glycerophospholipid metabolic processglycerolipid metabolic process meiosis I cell cycle process endoplasmic reticulum organization cell surface receptor signaling pathway heparan sulfate proteoglycanbiosynthetic process organic substance metabolic process organelle fission axonemal dynein complex assembly chondroitin sulfate biosynthetic process amide biosynthetic process organic cyclic compound biosynthetic biosynthetic process myofibril assembly glucocorticoid secretion purine-containing compoundprocess metabolic immune system development glycosaminoglycan metabolic process membrane lipidphospholipid biosynthetic catabolic processmonosaccharide process metabolic process chordate embryonic development vacuole organization microtubule bundle formation cell cycle response to other organism adaptive thermogenesis urogenital system development centripetally migrating follicle cell cell-cell fusion establishment of spindle localization netrin-activated signaling pathway metabolic process cellular nitrogen compoundcellular biosyntheticbiosynthetic processprocesscarbohydrate catabolic process mitochondrial fission spindle localization transmembrane transport nucleotide-sugar transmembrane process utilizing autophagic mechanism autophagy pentose metabolic process vasculature development glial cell differentiation striated muscle cell differentiation sulfur compound metabolic process migration multicellular organismal homeostasis microtubule-based process carbohydrate derivative transport RNA catabolic process sulfur compound biosynthetic process process alpha-amino acid biosynthetic process D-xylose metabolic process embryo development ending in birth or membrane fission cilium-dependent cell motility secretion by cell transport proteoglycan metabolic process cellular amino acid biosynthetic process phosphatidylinositol metabolic process hormone secretion primary metabolicorganonitrogen process compound biosyntheticorganophosphate catabolic process egg hatching striated muscle cell development meiotic cell cycle process sister chromatid segregation protein-DNA complex assembly signal transduction receptor guanylyl cyclase signaling pigment metabolic process nucleobase-containing compound monosaccharide biosynthetic process cell division tissue homeostasis protein-containing complex assembly process monosaccharide catabolic process maintenance of location organic hydroxy compound transport pathway metabolic process blastocyst development multi-organism behavior microtubule organizing center phagocytosis corticosterone secretion macromolecule catabolic processsulfur amino acid metabolic process cardiovascular system development male meiotic nuclear division chromosome segregation nucleosome organizationsignal release exocytosis organic substance biosynthetic process serine family amino acid metabolic hematopoietic or lymphoid organ blastocyst formation mitochondrion organization organization central nervous system development embryonic hemopoiesis actin-mediated cell contraction iron-sulfur cluster assembly aromatic compound biosynthetic process process renal system development cerebellum development development syncytium formation cellular macromolecule catabolic hepaticobiliary system development endomembrane system organization carbohydrate metabolic process glycolytic process oocyte microtubule cytoskeletonasymmetric cell division adaptation of rhodopsin mediated process biosynthetic process spinal cord developmenthead development hemocyte migration ovarian fusome organization telomere maintenance enzyme linked receptor protein signaling protein processing DNA catabolic process proteoglycan biosynthetic process aminoglycan metabolic process purine-containing compound secretion defense response to other organism cellular response to stress glycosaminoglycan biosynthetic process sulfur amino acid biosynthetic process organization ensheathment of neurons cell populationestablishment proliferation of chromosome signaling signaling heterocycle biosynthetic process biosynthetic process blood vessel development nervous system development cellular processcell-cell signaling pathway generation of precursor metabolites and meiotic cell cycle axoneme assembly localization metallo-sulfur cluster assembly corticosteroid hormone secretion protein catabolic process cellular carbohydrate metabolic process phospholipid metabolic process organelle organization chromosome localization cysteine metabolic process brainstem development vesicle targeting cell communication energy exocrine system development embryonic axis specification spermatogenesis ovarian follicle cell migration cilium or flagellum-dependent cell brain development metencephalon development angiogenesis fusome organization protein-DNA complex subunit response to iron ion starvation N-glycan processing peptide biosynthetic process nucleobase-containing small molecule liver development root system development establishment of vesicle localization immune response glycoprotein metabolic process oogenesis cystoblast division multi-organism reproductiveperoxisome process organization motility regulation of respiratory gaseous organic substance transport metabolic processcarbohydrate biosynthetic process serine family amino acid biosynthetic circulatory system development membrane organization cytoplasmic actin-based contraction organization regulation of blood vessel size DNA catabolic process, endonucleolytic aminoglycan biosynthetic process purine nucleotide metabolic process hexose metabolic process system development female gamete generation organelle assembly Golgi organization exchange by neurological system response to starvation cellular response to DNA damage process embryonic organ development anatomical structure formation involved cellular component assembly involved in involved in cell motility mRNA metabolic process phosphoruscarbohydrate metabolic derivative process metabolic L-serine metabolic process glomerulus development neural tube developmentmuscle cell differentiation process innate immune response ATP metabolic process organophosphate metabolic process ability . in morphogenesis actin filament-based movement stimulus chaperone-mediated autophagy process oligosaccharide-lipid intermediate oocyte development ameboidal-type cell migration morphogenesis cellular component organization establishment of organelle nucleosomelocalization assembly cellular response to nutrient levels glycosylation cellular carbohydrate biosynthetic cysteine biosynthetic process salivary gland development kidney development germarium-derived egg chamber transport nitrogen compound transporttelomere organization male gamete generation plastid organizationplastoglobule organization biological_process nucleobase-containing compound process biosynthetic process hexose catabolic process embryo development muscle cell development formation chloroplast organization receptor metabolic process protein metabolic process hindbrain development cellular component assembly intermembrane lipid transfer inflammatory response proteolysis prenylation biosynthetic process nephron development spermatid development epithelial cell migration cell-cell signaling involved in cell fate JNK cascade cyclic purine nucleotidecGMP metabolic metabolic process skeletal system development membrane docking stress-activated protein kinase signaling carbohydrate derivative biosynthetic purine nucleotidepurine biosynthetic ribonucleotide process metabolic process formation of primary germ layer retina homeostasis steroid hormone secretion cellular macromoleculemethylation metabolic glycoprotein biosynthetic process process forebrainmushroom development body development commitment organelle localization chromosome organization amide transport cascadeprotein targeting to vacuole involved in ATP generation from ADP gland development blood vessel morphogenesisgastrulation spermatid differentiationoocyte differentiationoocyte construction cell migration vesicle localization nucleobase-containinghistone exchange compound process process organophosphate biosynthetic process embryonic patternaxis specification specification cellular process involved in reproduction lipid transport G protein-coupled receptor signaling autophagy polysaccharide metabolic process mannose metabolic process cell differentiation presynapse assembly presynapse organization transmembrane receptor protein nucleic acid phosphodiester bond nucleic acid metabolic process cysteine biosynthetic process from in multicellular organism transport pathway stress-activated MAPK cascade macromolecule metabolic process anatomical structure development presynaptic membrane organization tyrosine kinase signaling pathway DNA metabolic process purine ribonucleotide biosynthetic establishment of localization in cell defense response hydrolysis DNA biosyntheticcellular process protein catabolic process serine heart development ovarian follicle cell developmentneuron differentiationcell fate commitment ciliary basal body-plasma membrane protein-containing microtubule-basedcomplex subunit movement endocrine hormone secretion chaperone-mediated protein transport cellular macromolecule biosyntheticmacromolecule biosynthetic processamino acid activationnucleotide-sugar metabolic process process animal organ development germ cell development import intovesicle-mediated cell transport signal transduction by protein cellular polysaccharide metabolic polysaccharide biosynthetic process ribose phosphate metabolic process cGMP biosynthetic process plant organ development synapse assembly docking cellular component organizationorganization or apoptotic signaling pathway involved in chaperone-mediated embryonic body morphogenesis cell fate commitment involved in postsynapse assembly cell motility cellular response to extracellular cellular response to heat phosphorylation process process ribonucleotide metabolic process salivary gland morphogenesis liver regeneration sensory system development sexual reproduction chromatin organization DNA repair protein maturation galactose metabolic process root development formation of primary germ layer reproduction biogenesis localization vacuolar transportstimulus autophagy ADP metabolic process tube development postsynapse organization chromatin assembly maintenance of location in cell protein targeting to lysosome involved in ribose phosphate biosynthetic process muscle structure developmentreproductive systemembryonic development morphogenesis ectodermal cell differentiation membrane assembly organelle localization by membrane chromatin assembly or disassembly protein transmembrane transport nucleoside phosphate metabolic process gamete generation reproductive process chaperone-mediated autophagy modification-dependent macromolecule ribonucleotide biosynthetic process neural retina development ectoderm formation developmental maturation pollen sperm cell differentiationdevelopmental process cilium assembly tethering synaptic vesiclepolytene cycle chromosome puffing peptide transport cellular heat acclimation nucleoside phosphate biosynthetic DNA replication catabolic process cellular polysaccharide biosynthetic cyclic nucleotide biosynthetic process cartilage development ectodermal cell fate commitment transposition heat shock-mediated polytene xenobiotic metabolic process phosphate-containing compoundprocess cellular developmental process presynaptic membrane assembly extracellular structure organization DNA double-strand break processingDNA integration insulin metabolic process nucleotide-sugar biosynthetic process nucleotide metabolic process localization of cell chromosome puffing process metabolic process cellular component morphogenesis lateral inhibition DNA conformation change MAPK cascade gland morphogenesis respiratory system development body morphogenesis developmental process involved in growth synaptic vesicle recycling lysosomal transport DNA-dependent DNA replication nucleotide biosynthetic process galactose catabolic processcyclic nucleotide metabolic process pattern specification process epithelium migration multicellular organism reproduction synapse organization response to external biotic stimulus DNA-templated transcription, initiation somatic muscle development cell maturation reproduction establishment of localization ATP-dependent chromatin remodeling intracellular signal transduction proteasomal protein catabolic process peptidyl-lysine modification to adipose tissue development plant organ morphogenesis anatomical structure maturation cell death RNA biosyntheticcellular process protein metabolic process post-embryonic animal organ multicellular organism development rhythmic process vascular endothelial growth factor RNA-dependent DNA biosynthetic peptidyl-hypusine dolichol-linked oligosaccharide anatomical structure morphogenesis fertilization substrate-dependent cell migration movement of cell or subcellular lipid localization vesicle-mediated transport in synapse cellular response to stimulus transposition, DNA-mediated transcription initiation from RNA development epithelium development columnar/cuboidal epithelial cell postsynaptic specializationcell assemblypostsynaptic projection assembly specialization organization double-strand break repair process extracellular polysaccharide metabolic biosynthetic process placenta development aging cell fate determination photoreceptor cell maintenance component cellular localization Golgi vesicle transportchaperone-mediated protein transport receptor signaling pathway DNA-dependent DNA replication polymerase II promoter macromolecule glycosylation animal organ regenerationretina development in camera-type eye epithelial cell differentiation development heat acclimation proteolysis involved in cellular protein translation nucleoside diphosphate phosphorylation heart morphogenesis postsynaptic membranecellular organization component maintenance synaptonemal complex organizationmaintenance of protein location presynaptic endocytosis light adaption response to nutrient levels maintenance of fidelity process extracellular matrix organization interstrand cross-link repair catabolic process purine ribonucleoside diphosphate ectoderm developmentplant epidermal cell differentiation seed trichome differentiation postsynaptic membrane assembly cellular component disassembly endocytosis transcription, DNA-templated muscle organ developmentanimal organ morphogenesis cell growth RNA metabolic process metamorphosis reproductive structure developmenttrichome differentiation inhibitory synapse assembly microtubule-based transport chromatin remodeling phototransduction response to heat sugar mediated signaling pathway non-recombinational repair metabolic process root morphogenesis nucleic acid transport DNA recombination tube morphogenesis ectodermal cell fate determination mating DNA packaging extracellular polysaccharide biosynthetic nucleoside diphosphate metabolic cell development tissue migration cellular component biogenesis protein targeting to vacuole carbohydrate mediated signaling protein prenylation seed trichome elongation membrane ciliumbiogenesis organization locomotion endosomal transportrhodopsin mediated signalingresponse pathway to extracellular stimulus protein modification process protein glycosylation connective tissue development maintenance of cell number multicellular organismal reproductive transposition, RNA-mediated mRNA processing nucleic acid-templatedmacromolecule transcription modification process process visual system development regeneration excitatory synapse assemblycell projection organization vascular process in circulatoryblood system circulation protein targeting to lysosome gene expression process intracellular transport response to biotic stimulus macromolecule methylation protein N-linked glycosylation larval somatic muscle development multicellular organism aging single fertilization response to stress covalent chromatin modification phosphorylation sensory organ development columnar/cuboidal epithelial cell double-strand break repair via transcription by RNA polymerase II larval development epithelial cell development endocrine processmacromolecule localization cellular response to external stimulus protein phosphorylation differentiation protein transport nonhomologous end joining nucleotide phosphorylation tissue development developmental growth plasma membrane boundedprogrammed cell cell deathcell recognition synaptonemal complexapoptotic disassembly process microgametogenesisvegetative to reproductive phase multicellular organismalcell part processmorphogenesis response to ischemia purine nucleoside diphosphate plant epidermis development post-embryonic development projection assembly retrograde transport, endosome to Golgi modification-dependent protein tRNA aminoacylation chaeta development camera-type eye development transition of meristem sperm-egg recognition cytosolic transport intra-Golgi vesicle-mediated transport programmed cell death involved in cell maintenance of synapse structure synaptic vesicle endocytosis replication fork processing catabolic process dephosphorylation metabolic process trichoblast maturationseed development substrate-dependent cell migration, cell mitochondrial transcription ribonucleoside diphosphate metabolic development ovulation cycle establishment of RNA localization response to cold second-messenger-mediated signaling DNA-templated transcription, elongation skeletal muscle organ development open tracheal system development root epidermal cell differentiation tissue morphogenesis extension neuron death process morphogenesis of a branching structure cell morphogenesis neuromuscular junction development protein-containing complex disassembly microtubule-based protein transportreceptor-mediatedprotein transmembraneendocytosis import into determination of adult lifespan mitochondrial RNAprotein metabolic quality process control forproteasome-mediated misfolded or unidimensional cell growth cell-cell recognition response to wounding intracellular organelle response to hypoxia epithelial tube morphogenesis stem cell population maintenance postsynaptic density assembly establishment of protein localization incompletelyubiquitin-dependent synthesized proteins protein catabolic gametophyte developmentphotoreceptor cell differentiation postsynaptic density organization response to stimulus cellular response to topologically sensory organ morphogenesis fruit development tissue regeneration protein folding cytoskeleton-dependent intracellular protein targeting cellular response to environmental process morphogenesis of an epithelium incorrect protein tRNA aminoacylation for protein developmental growth involved in developmental cell growth RNA localizationcellular macromolecule localization transport response to external stimulus stimulus mesoderm development cell projection morphogenesis postsynaptic density protein 95 maintenance of protein location in vesiclecell uncoating phototransduction, visible light intron homing translation morphogenesis wound healing mitochondrial gene expression clustering intraciliary transport RNA transport cellular response responseto oxidative to stresstemperature stimulus cytoplasm protein quality control by the protein autophosphorylation branching morphogenesis of an organ growth behavior system process protein dephosphorylation eye development cell morphogenesis involved in plasma membrane bounded cell circulatory system process cellular detoxification mRNA splicing, via spliceosomeubiquitin-proteasome system epithelial tube root hair cell development protein localization to lysosome morphogenesis of a branching differentiation multicellular organism growth projection organization detoxification peptidyl-lysine modification muscle tissue development neuron development transcription elongationRNA from modification cellular protein modification process skeletal muscle tissue development pollen development reproductive behaviorphotoperiodism, flowering protein localization response to osmotic stress small GTPase mediated signal RNA processing histone modification root hair cell differentiationepithelium binding of sperm to zona pellucida neuron apoptotic process intracellular protein transport mitochondrial promoter protein methylation trichoblast differentiation ribonucleoprotein complex biogenesis establishment of protein localization to transduction protein transport along microtubuletransport along microtubule cellular response to misfolded proteincyclic-nucleotide-mediated signaling maintenance of postsynaptic vacuole response to decreased oxygen levels ubiquitin-dependent protein catabolic seed germination ossification glial cell apoptotic process specialization structure protein import response to mechanical stimulus homing of group II introns cellular response to unfolded protein process seedling development response to light intensity tropism response to salt stress striated muscle tissue development branching involved in open tracheal root hair elongation digestion lamellipodium assembly cellular protein complex disassembly synaptic vesicle uncoating tRNA metabolic process system development estrous cycle chaperone-mediated autophagy eye morphogenesis retinal cell programmed cell death detection of light stimulus adult behavior gephyrin clustering translocationinvolved in complex disassembly protein-containing complex localization cellular response to xenobiotic stimulus detection of external stimulusdetection of stimulus response to oxidative stress ncRNA metabolic process RNA methylation fin regeneration postsynaptic density assembly nuclear transport protein depolymerization establishmenttaxis of protein localization to response to oxygen levels histone H2A acetylation eye photoreceptor cell differentiation cell tip growth mating behavior protein localization to synapse response to activity cGMP-mediated signaling histone acetylation multicellular organismal movement organelle hyperosmotic response protein alkylationhistone methylation photoreceptor cell development cellular protein localization response to abiotic stimulus response to topologically incorrect methionyl-tRNA aminoacylation detection of visible light peptidyl-lysine acetylation plasma membrane bounded cell visual behavior protein localization to membrane protein response to misfolded protein compound eye development lamellipodium organization vocalization behavior gravitropism pseudouridine synthesis projection morphogenesis peptidyl-amino acid modification root hair cell tip growth neuron projection development nervous system process clathrin coat disassembly RNA splicing, via transesterification peptidyl-lysine methylation histone H4 acetylation response to unfolded protein cell morphogenesis involved in neuron protein localization to vacuole reactions with bulged adenosine as RNA splicing protein hydroxylation compound eye morphogenesis response to nutrient ubiquitin-dependent protein catabolic cellular response to light stimulus detection of abiotic stimulus nucleophile compound eye retinal cell programmed differentiation neuron recognition tRNA processing neuron projection extension locomotory behavior ribosome biogenesis cellular response to abiotic stimulusresponse to electrical stimulus process via the multivesicular body photoperiodismneuron projection guidance dsRNA transport response to light stimulus rRNA metabolic process protein acylation cell death exploration behavior responsecellular to pH response to carbohydrate tRNA modification sorting pathway chaperone-mediated protein folding cellular detoxification of aldehyde RNA 3'-end processing histoneinternal lysine methylation peptidyl-lysine acetylation histone H4-K16 acetylation eye photoreceptor cell development response to gravity stimulus primary branching, open tracheal system 'de novo' protein folding protein import into nucleus long-day photoperiodism, flowering response to radiation histone H3-K4 methylation neuron projection morphogenesis axo-dendritic transport ncRNA processing cellular response to reactive oxygen response to acidic pH musculoskeletal movement cellular response to radiation protein acetylation courtship behavior thigmotaxis cellular responsespecies to chemical stimulus snRNA metabolic process nucleocytoplasmic transport cellular response to pH maintenance of protein localization in Ras protein signal transduction peptidyl-lysine dimethylation adult locomotory behavior response to endogenous stimulus RNA splicing, via transesterification axon development long-day photoperiodism cellular response to toxic substance tRNA methylation histone H3-K36 methylation male mating behavior organelle protein localization to organelle reactions cognition axonogenesis locomotory exploration behavior peptidyl-proline modification cellular response to acidic pH learning or memory response to xenobioticcellular stimulus response to organic substance internal protein amino acid acetylation chemotaxis protein modification by small protein axon extension Rac protein signal transduction dendrite extension chaperone cofactor-dependent protein conjugation or removal import into nucleus cellular response to aldehyde refolding responseresponse to vitaminto reactive oxygen species cellular response to acid chemical histone H3-K36 dimethylation axon guidance 'de novo' posttranslational protein folding protein localization to nucleus ncRNA 3'-end processing visual learning slow axonal transport cellular response to endogenous male courtship behavior neuromuscular process axonal defasciculation cellular response to oxygen-containing stimulus axon choice point recognition response tocellular toxic substance response to hydrogen peroxide snRNA processing compound responsecellular to chemicalresponse tocellular antibiotic response to nitrogen compound response to UV cellular response to UV Rho protein signal transduction cellular response to organic cycliccellular response to methanol protein peptidyl-prolyl isomerization jump response cellular response to benomyl tRNA nucleoside ribose methylation protein localization to endoplasmic compoundcellular response to alcohol reticulum cellular response to drug response to organic substance chemotaxis to folate response to antibiotic cellular response to organonitrogen cellular response to hormone stimulus learning maintenance of protein localization in response to carbohydrate chemotaxis to cAMP response to acid chemical compound endoplasmic reticulum snRNA 3'-end processing motor neuron axon guidance response to hydrogen peroxideresponse to nitrogen compound protein localization to endosome Cdc42 protein signal transduction defasciculation of motor neuron axon neuromuscular process controlling response to folic acid response to hormone associative learning balance response to odorant response to methanol response to alcohol axon midline choice point recognition memory response to amphetamine response to oxygen-containing response to ethanol cellular response to peptide wobble position ribose methylation sensory perception compound response to fungicide response to UV-C response to lipid cellular response to UV-C cellular response to inorganic substance response to auxin response to organic cyclicresponse compound to organophosphorus response to drug response to arsenic-containing response to benomyl response to organonitrogen compound substance U2 snRNA 3'-end processing protein modification by small protein protein retention in ER lumen response to estradiol conjugation response to ketone cellular response to peptideresponse hormone to monosaccharide stimulus protein localization to early endosome response to steroid hormone response to arsenite ion response to cAMP long-term memory sensory perception of pain response to inorganic substance response to chitin response to peptide

response to bronchodilator response to progesterone response to peptide hormone response to amine

response to purine-containing compound response to hexose sensory perception of chemicalsensory perceptionstimulus of light stimulus cellular response to insulin stimulus

cellular response to metal ion

response to selenium ion response to glucose response to insulin protein ubiquitination

sensory perception of smell visual perception

response to metal ion

cellular response to cadmium ion protein autoubiquitination protein monoubiquitination

response to nickel cation

protein polyubiquitination response to cadmium ion response to copper ion

protein K48-linked ubiquitination

protein K63-linked ubiquitination Genomic approaches enhance phytosanitary research and regulation: using genomics to protect our forests from gypsy moths Gwylim Blackburn, Natural Resources Canada, Canadian Forest Service, Victoria, BC [email protected]

Summary • Biological Invasion: - Widespread, expanding, and costly - Phytosanitary research and regulation is aimed at limiting its impact • Genomics: - Accessible for any species and ready for widespread uptake - Can enhance our understanding of the entire process of BI, strengthening phytosanitary research and regulation Thank you! Merci!