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targets (2) enzymes (10)
for drugs
Identification
Name Isoniazid
Accession Number DB00951 (APRD01055, EXPT01940)
Type small molecule
Groups approved
Description

Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • HIA
  • Hydrazid
  • Hydrazide
  • INH
  • Isohydrazide
  • Isonicotinhydrazid
  • Isonicotinic acid hydrazide
  • Isonicotinic hydrazide
  • Isonicotinohydrazide
  • Isonicotinoyl hydrazide
  • Isonicotinyl hydrazide
  • Isonicotinyl hydrazine
  • Isonicotinylhydrazine
Brand names
  • Andrazide
  • Antimicina
  • Antituberkulosum
  • Armacide
  • Armazid
  • Armazide
  • Atcotibine
  • Azuren
  • Bacillin
  • Cedin
  • Cemidon
  • Chemiazid
  • Chemidon
  • Cortinazine
  • Cotinazin
  • Cotinizin
  • Defonin
  • Dibutin
  • Diforin
  • Dinacrin
  • Ditubin
  • Ebidene
  • Eralon
  • Ertuban
  • Eutizon
  • Evalon
  • Fimalene
  • FSR 3
  • GINK
  • Hidranizil
  • Hidrasonil
  • Hidrulta
  • Hidrun
  • Hycozid
  • Hyozid
  • Hyzyd
  • Ido-tebin
  • Idrazil
  • Inah
  • Inizid
  • Iscotin
  • Isidrina
  • Ismazide
  • Isobicina
  • Isocid
  • Isocidene
  • Isocotin
  • Isolyn
  • Isonerit
  • Isonex
  • Isoniacid
  • Isoniazid SA
  • Isoniazide
  • Isonicazide
  • Isonicid
  • Isonico
  • Isonicotan
  • Isonicotil
  • Isonide
  • Isonidrin
  • Isonikazid
  • Isonilex
  • Isonin
  • Isonindon
  • Isonirit
  • Isoniton
  • Isonizide
  • Isopyrin
  • Isotamine
  • Isotebe
  • Isotebezid
  • Isotinyl
  • Isozide
  • Isozyd
  • Laniazid
  • Laniozid
  • Mybasan
  • Neo-Tizide
  • Neoteben
  • Neoxin
  • Neumandin
  • Nevin
  • Niadrin
  • Nicazide
  • Nicetal
  • Nicizina
  • Niconyl
  • Nicotibina
  • Nicotibine
  • Nicotisan
  • Nicozide
  • Nidaton
  • Nidrazid
  • Nikozid
  • Niplen
  • Nitadon
  • Nydrazid
  • Nyscozid
  • Pelazid
  • Percin
  • Phthisen
  • Pycazide
  • Pyreazid
  • Pyricidin
  • Pyridicin
  • Pyrizidin
  • Raumanon
  • Razide
  • Retozide
  • Rifamate
  • Rimicid
  • Rimifon
  • Rimiphone
  • Rimitsid
  • Robiselin
  • Robisellin
  • Roxifen
  • Sanohidrazina
  • Sauterazid
  • Sauterzid
  • Stanozide
  • TB-Phlogin
  • TB-Razide
  • TB-Vis
  • Tebecid
  • Tebenic
  • Tebexin
  • Tebilon
  • Tebos
  • Teebaconin
  • Tekazin
  • Tibazide
  • Tibemid
  • Tibison
  • Tibivis
  • Tibusan
  • Tubazid
  • Tubazide
  • Tubeco
  • Tubecotubercid
  • Tuberian
  • Tubicon
  • Tubilysin
  • Tubomel
  • Tyvid
  • Unicocyde
  • Unicozyde
  • Vazadrine
  • Vederon
  • Zidafimia
  • Zinadon
  • Zonazide
Brand name mixtures
  • Isotamine B 300 (Isoniazid + Pyridoxine Hydrochloride)
  • Rifater (Isoniazid + Pyrazinamide + Rifampin)
Categories
  • Antitubercular Agents
  • Fatty Acid Synthesis Inhibitors
CAS number 54-85-3
Weight Average: 137.1393
Monoisotopic: 137.058911861
Chemical Formula C6H7N3O
InChI Key InChIKey=QRXWMOHMRWLFEY-UHFFFAOYSA-N
InChI
InChI=1S/C6H7N3O/c7-9-6(10)5-1-3-8-4-2-5/h1-4H,7H2,(H,9,10)
Plain Text
IUPAC Name
pyridine-4-carbohydrazide
SMILES
NNC(=O)C1=CC=NC=C1
Plain Text
Mass Spec show (8.2 KB)
Taxonomy
Kingdom Organic
Classes
  • Pyridines and Derivatives
Substructures
  • Carboxylic Acids and Derivatives
  • Amino Ketones
  • Pyridines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Hydrazine Derivatives
Pharmacology
Indication For the treatment of all forms of tuberculosis in which organisms are susceptible.
Pharmacodynamics Isoniazid is a bactericidal agent active against organisms of the genus Mycobacterium, specifically M. tuberculosis, M. bovis and M. kansasii. It is a highly specific agent, ineffective against other microorganisms. Isoniazid is bactericidal to rapidly-dividing mycobacteria, but is bacteriostatic if the mycobacterium is slow-growing.
Mechanism of action Isoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.
Absorption Readily absorbed following oral administration; however, may undergo significant first pass metabolism. Absorption and bioavailability are reduced when isoniazid is administered with food.
Volume of distribution Not Available
Protein binding Very low (0-10%)
Metabolism

Primarily hepatic. Isoniazid is acetylated by N -acetyl transferase to N -acetylisoniazid; it is then biotransformed to isonicotinic acid and monoacetylhydrazine. Monoacetylhydrazine is associated with hepatotoxicity via formation of a reactive intermediate metabolite when N-hydroxylated by the cytochrome P450 mixed oxidase system. The rate of acetylation is genetically determined. Slow acetylators are characterized by a relative lack of hepatic N -acetyltransferase.
Route of elimination From 50 to 70 percent of a dose of isoniazid is excreted in the urine within 24 hours.
Half life Fast acetylators: 0.5 to 1.6 hours. Slow acetylators: 2 to 5 hours.
Clearance Not Available
Toxicity LD50 100 mg/kg (Human, oral). Adverse reactions include rash, abnormal liver function tests, hepatitis, peripheral neuropathy, mild central nervous system (CNS) effects. In vivo, Isoniazid reacts with pyridoxal to form a hydrazone, and thus inhibits generation of pyridoxal phosphate. Isoniazid also combines with pyridoxal phosphate; high doses interfere with the coenzyme function of the latter.
Affected organisms
  • Mycobacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Sandoz canada inc
  • Sandoz inc
  • Hoffmann la roche inc
  • Carolina medical products co
  • Mikart inc
  • Lannett co inc
  • Dow pharmaceutical corp sub dow chemical co
  • Medpointe pharmaceuticals medpointe healthcare inc
  • Novartis pharmaceuticals corp
  • Barr laboratories inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Halsey drug co inc
  • Impax laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Eli lilly and co
  • Mk laboratories inc
  • Mutual pharmaceutical co inc
  • Nexgen pharma inc
  • Panray corp sub ormont drug and chemical co inc
  • L perrigo co
  • Pharmavite pharmaceuticals
  • Phoenix laboratories inc
  • Purepac pharmaceutical co
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • Whiteworth towne paulsen inc
  • Bristol myers squibb co
  • Everylife
Packagers
Dosage forms
Form Route Strength
Powder Oral
Syrup Oral
Tablet Oral
Prices
Unit description Cost Unit
Isoniazid 100 mg/ml vial 27.37 USD ml
Rifamate 150-300 mg capsule 4.36 USD capsule
Rifamate capsule 4.19 USD capsule
Isoniazid 100 mg tablet 0.28 USD tablet
Isoniazid 300 mg tablet 0.18 USD tablet
Isoniazid 50 mg/5ml Syrup 0.16 USD ml
Isoniazid powder 0.11 USD g
Patents Not Available
Properties
State solid
Melting point 171.4 oC
Experimental Properties
Property Value Source
water solubility 140 mg/mL PhysProp
logP -0.8 PhysProp
logS 0.01 [ADME Research, USCD] PhysProp
pKa 1.82 Various sources
Predicted Properties
Property Value Source
water solubility 3.49e+01 g/l ALOGPS
logP -0.71 ALOGPS
logP -0.69 ChemAxon Molconvert
logS -0.59 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 68.01 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 37.46 ChemAxon Molconvert
polarizability 13.21 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00346 Link_out
KEGG Compound C07054 Link_out
PubChem Compound 3767 Link_out
PubChem Substance 46506039 Link_out
ChemSpider 3635 Link_out
ChEBI 6030 Link_out
ChEMBL 6030 Link_out
Therapeutic Targets Database DAP000011 Link_out
PharmGKB PA450112 Link_out
HET ISZ Link_out
Drug Product Database 577782 Link_out
RxList http://www.rxlist.com/cgi/generic2/isoniaz.htm Link_out
Drugs.com http://www.drugs.com/cdi/isoniazid.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Isoniazid Link_out
ATC Codes
  • J04AC01
AHFS Codes
  • 08:16.04
PDB Entries Not Available
FDA label Not Available
MSDS show (73.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid aged foods (cheese, red wine), pickled foods, cured foods (bacon/ham), chocolate, fava beans, beer, unless approved by your physician.
  • Avoid alcohol.
  • Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.
  • Increase dietary intake of magnesium, folate, vitamin B6, B12, and/or consider taking a multivitamin.
  • Take on empty stomach: 1 hour before or 2 hours after meals.
  • Take with a full glass of water.
Targets

1. Peroxidase/catalase T

Pharmacological action: yes
Actions: other/unknown

Bifunctional, exhibiting both a catalase and broad- spectrum peroxidase activities. May play a role in the intracellular survival of mycobacteria

Organism class: bacterial
UniProt ID: Q08129 Link_out
Gene: katG
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Pym AS, Domenech P, Honore N, Song J, Deretic V, Cole ST: Regulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity and virulence by furA of Mycobacterium tuberculosis. Mol Microbiol. 2001 May;40(4):879-89. Pubmed
  4. Heym B, Alzari PM, Honore N, Cole ST: Missense mutations in the catalase-peroxidase gene, katG, are associated with isoniazid resistance in Mycobacterium tuberculosis. Mol Microbiol. 1995 Jan;15(2):235-45. Pubmed
  5. Wilson TM, de Lisle GW, Collins DM: Effect of inhA and katG on isoniazid resistance and virulence of Mycobacterium bovis. Mol Microbiol. 1995 Mar;15(6):1009-15. Pubmed
  6. Vilcheze C, Jacobs WR Jr: The mechanism of isoniazid killing: clarity through the scope of genetics. Annu Rev Microbiol. 2007;61:35-50. Pubmed

2. Enoyl-[acyl-carrier-protein] reductase [NADH]

Pharmacological action: yes
Actions: adduct

Involved in the resistance against the antituberculosis drugs isoniazid and ethionamide

Organism class: bacterial
UniProt ID: P0A5Y6 Link_out
Gene: inhA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Schroeder EK, Basso LA, Santos DS, de Souza ON: Molecular dynamics simulation studies of the wild-type, I21V, and I16T mutants of isoniazid-resistant Mycobacterium tuberculosis enoyl reductase (InhA) in complex with NADH: toward the understanding of NADH-InhA different affinities. Biophys J. 2005 Aug;89(2):876-84. Epub 2005 May 20. Pubmed
  4. Wilson TM, de Lisle GW, Collins DM: Effect of inhA and katG on isoniazid resistance and virulence of Mycobacterium bovis. Mol Microbiol. 1995 Mar;15(6):1009-15. Pubmed
  5. Broussy S, Coppel Y, Nguyen M, Bernadou J, Meunier B: 1H and 13C NMR characterization of hemiamidal isoniazid-NAD adducts as possible inhibitors of InhA reductase of Mycobacterium tuberculosis. Chemistry. 2003 May 9;9(9):2034-8. Pubmed
  6. Vilcheze C, Jacobs WR Jr: The mechanism of isoniazid killing: clarity through the scope of genetics. Annu Rev Microbiol. 2007;61:35-50. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2E1

Actions: substrate, inhibitor, inducer

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C9

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 1A2

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2D6

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C19

Actions: inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Arylamine N-acetyltransferase 2

Actions: substrate

Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens

UniProt ID: P11245 Link_out
Gene: NAT2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Upton AM, Mushtaq A, Victor TC, Sampson SL, Sandy J, Smith DM, van Helden PV, Sim E: Arylamine N-acetyltransferase of Mycobacterium tuberculosis is a polymorphic enzyme and a site of isoniazid metabolism. Mol Microbiol. 2001 Oct;42(2):309-17. Pubmed

8. Arylamine N-acetyltransferase

Actions: inhibitor
UniProt ID: P0A5L8 Link_out
Gene: nat
SNPs: SNPJam Report Link_out

References:
  1. Upton AM, Mushtaq A, Victor TC, Sampson SL, Sandy J, Smith DM, van Helden PV, Sim E: Arylamine N-acetyltransferase of Mycobacterium tuberculosis is a polymorphic enzyme and a site of isoniazid metabolism. Mol Microbiol. 2001 Oct;42(2):309-17. Pubmed

9. Cytochrome P450 2A6

Actions: inhibitor

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase

UniProt ID: P11509 Link_out
Gene: CYP2A6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

10. Cytochrome P450 2C8

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:44

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.