Claims for Patent: 8,014,953

Summary for Patent: 8,014,953

Title:	RNA surveillance among curated proteins
Abstract:	Computational methods for systematically characterizing putative protein isoforms as apparent targets of nonsense-mediated decay (NMD) comprise: (a) identifying a dataset of target putative protein isoform sequences for characterization; (b) identifying from an mRNA dataset corresponding mRNA sequences representing transcripts encoding the protein isoforms; (c) determining corresponding gene intron-exon structures by mapping the mRNA sequences to corresponding genomic sequences; and (d) determining if the transcripts are apparent targets of NMD. Methods for regulating the expression of a gene encoding a protein isoform characterized as an apparent target of NMD comprise biasing expression of the isoform by modulating transcript splicing or modulating NMD activity.
Inventor(s):	Brenner; Steven E. (Berkeley, CA), Green; Richard E. (Berkeley, CA), Hillman; R. Tyler (Berkeley, CA)
Assignee:	The Regents of the University of California (Oakland, CA)
Application Number:	10/637,482
Patent Claims:	1. A method for systematically characterizing putative protein isoforms as apparent targets of nonsense-mediated decay (NMD), the method comprising the following steps, each of which is performed with a suitably programmed computer: identifying a dataset of target putative protein isoform sequences from a curated protein sequence database for characterization; identifying from an mRNA dataset corresponding mRNA sequences representing transcripts encoding the protein isoforms, wherein each of the transcripts comprises a termination codon and a final intron; determining corresponding gene intron-exon structures by mapping the mRNA sequences to corresponding genomic sequences; determining if the transcripts are apparent targets of NMD by comparing the position of the termination codon to the position of the final intron, wherein if the termination codon of the transcript is more than 50 nucleotides upstream of the final intron position, then the transcript is an apparent target of NMD; and outputting from the computer a list of said isoforms that are apparent targets of NMD, wherein the dataset of target putative protein isoform sequences comprises a subset of the isoforms of Table 1: TABLE-US-00002 TABLE 1 Protein isoforms characterized as targets of NMD, ISOFORM NAME ACCESSION PROTEIN DESCRIPTION 3BP2_HUMANISO P78314 SH3 domain-binding protein 2 FORM SHORT 5H4_HUMANMAJOR Q13639 5-hydroxytryptamine 4 ISOFORM receptor A1A1_HUMANISO P05023 Sodium/potassium-transporting FORM SHORT ATPase alpha-1 chain precursor ABCD_HUMANISO Q9NSE7 Putative ATP-binding cassette FORM 2 transporter C13 ABCD_HUMANISO Q9NSE7 Putative ATP-binding cassette FORM 3 transporter C13 AD11_HUMANISO O75078 ADAM 11 precursor FORM SHORT AD12_HUMANMAJOR O43184 ADAM 12 precursor ISOFORM AD22_HUMANISO Q9POK1 ADAM 22 precursor FORM 2 AKP1_HUMANISO Q92667 A kinase anchor protein 1 FORM 2 mitochondrial precursor ANPB_HUMANISO P20594 Atrial natriuretic peptide FORM SHORT receptor B precursor AS13_HUMANMAJOR Q8WXK3 Ankyrin repeat and SOCS box ISOFORM containing protein 13 AS13_HUMANISO Q8WXK3 Ankyrin repeat and SOCS box FORM 2 containing protein 13 ATF3_HUMANISO P18847 Cyclic-AMP-dependent FORM 2 transcription factor ATF-3 ATR_HUMANMAJOR Q9H6X2 Anthrax toxin receptor ISOFORM precursor B3G7_HUMANISO Q9NY97 Beta-1 3-galactosyltransferase FORM 2 7 BC12_HUMANISO Q9HB09 Bcl-2 related proline-rich FORM 2 protein BMP1_HUMANISO P13497 Bone morphogenetic protein 1 FORM BMP1-4 precursor BMP1_HUMANISO P13497 Bone morphogenetic protein 1 FORM BMP1-5 precursor BMP1_HUMANISO P13497 Bone morphogenetic protein 1 FORM BMP1-6 precursor C343_HUMANISO Q9HB55 Cytochrome P450 3A43 FORM 4 CA34_HUMANMAJOR Q01955 Collagen alpha 3 ISOFORM CA34_HUMANISO Q01955 Collagen alpha 3 FORM 3 CAL0_HUMANISO P01258 Calcitonin precursor [Contains: FORM 2 Calcitonin; Katacalcin CANA_HUMANISO Q9HC93 Calpain 10 FORM B CANA_HUMANISO Q9HC93 Calpain 10 FORM D CANA_HUMANISO Q9HC93 Calpain 10 FORM E CANA_HUMANISO Q9HC93 Calpain 10 FORM F CBS_HUMANMAJOR P35520 Cystathionine beta-synthase ISOFORM CD38_HUMANISO P28907 ADP-ribosyl cyclase 1 FORM 2 CD47_HUMANISO Q08722 Leukocyte surface antigen FORM OA3-305 CD47 precursor CFLA_HUMANISO O43618 CASP8 and FADD-like FORM 9 apoptosis regulator precursor CHRD_HUMANISO Q9P0Z5 Chordin precursor FORM 3 CHRD_HUMANISO Q9P0Z5 Chordin precursor FORM 4 CIQ2_HUMANISO O43526 Potassium voltage-gated FORM 3 channel subfamily KQT member 2 CIW4_HUMANISO Q9NYG8 Potassium channel subfamily FORM 2 K member 4 CLK1_HUMANISO P49759 Protein kinase CLK1 FORM SHORT CLK2_HUMANISO P49760 Protein kinase CLK2 FORM SHORT CLK3_HUMANISO P49761 Protein kinase CLK3 FORM 2 CML1_HUMANMAJOR Q99788 Chemokine receptor-like 1 ISOFORM COG4_HUMANISO Q9H9E3 Conserved oilgomeric Golgi FORM 2 complex component 4 COLQ_HUMANISO Q9UP88 Acetylcholinesterase FORM VII collagenic tail peptide precursor CPXM_HUMANISO Q96SM3 Potential carboxypeptidase X FORM 2 precursor CRN1_HUMANISO Q9NYD8 Crooked neck-like protein 1 FORM 4 CRN1_HUMANISO Q9NYD8 Crooked neck-like protein 1 FORM 5 CT24_HUMANISO Q9BUV8 Protein C20orf24 FORM 4 CTGF_HUMANMAJOR P29279 Connective tissue growth ISOFORM factor precursor CU07_HUMANISO P57077 Protein C21orf7 FORM B CU07_HUMANISO P57077 Protein C21orf7 FORM C CU18_HUMANISO Q9NVD3 Protein C21orf18 FORM B CU63_HUMANISO P58658 Protein C21orf63 precursor FORM B CU80_HUMANISO Q9Y2G5 Protein C21orf80 FORM B CYB5_HUMANISO P00167 Cytochrome b5 FORM 2 DACA_HUMANISO Q9BYJ9 Dermatomyositis associated FORM 2 with cancer putative autoantigen-1 DFFB_HUMANISO O76075 DNA fragmentation factor 40 FORM BETA kDa subunit DFFB_HUMANISO O76075 DNA fragmentation factor 40 FORM DELTA kDa subunit DFFB_HUMANISO O76075 DNA fragmentation factor 40 FORM GAMMA kDa subunit DJB2_HUMANMAJOR P25686 DnaJ homolog subfamily B ISOFORM member 2 DJB2_HUMANISO P25686 DnaJ homolog subfamily B FORM 3 member 2 DONS_HUMANISO Q9NYP3 Downstream of son gene FORM 2 protein DONS_HUMANIS Q9NYP3 Downstream of son gene OFORM 3 protein DPP3_HUMANISO Q9NY33 Dipeptidyl-peptidase III FORM 2 DSCA_HUMANISO O60469 Down syndrome cell adhesion FORM SHORT molecule precursor DTNB_HUMANISO O60941 Dystrobrevin beta FORM 3 EPA3_HUMANMAJOR P29320 Ephrin type-A receptor 3 ISOFORM precursor ERAL_HUMANISO O75616 GTP-binding protein era FORM HERA-B homolog ESR2_HUMANISO Q9UHD3 Estrogen receptor beta FORM 3 F263_HUMANMAJOR Q16875 6-phosphofructo-2- ISOFORM kinase/fructose-2 6- biphosphatase 3 FAFY_HUMANISO O00507 Probable ubiquitin carboxyl- FORM SHORT terminal hydrolase FAF-Y FCAR_HUMANISO P24071 Immunoglobulin alpha Fc FORM B-DELTA- receptor precursor S2 FCE2_HUMANMAJOR P06734 Low affinity immunoglobulin ISOFORM epsilon FC receptor FTCD_HUMANISO O95954 Formimidoyltransferase- FORM E cyclodeaminase FUT8_HUMANISO Q9BYC5 Alpha-(1,6)-fucosyltransferase FORM 2 FXM1_HUMANISO Q08050 Forkhead box protein M1 FORM 2 G72_HUMANMAJOR P59103 Protein G72 ISOFORM G72_HUMANISO P59103 Protein G72 FORM 2 G8_HUMANMAJOR Q9UBA6 G8 protein ISOFORM GBR1_HUMANISO Q9UBS5 Gamma-aminobutyric acid FORM 1E type B receptor subunit 1 precursor GCFC_HUMANISO Q9Y5B6 GC-rich sequence DNA- FORM D binding factor homolog GCP2_HUMANISO Q9BSJ2 Gamma-tubulin complex FORM 2 component 2 GDNR_HUMANISO P56159 GDNF receptor alpha FORM 2 precursor GLI2_HUMANMAJOR P10070 Zinc finger protein GLI2 ISOFORM GLI2_HUMANISO P10070 Zinc finger protein GLI2 FORM BETA GLI2_HUMANISO P10070 Zinc finger protein GLI2 FORM DELTA GLI2_HUMANISO P10070 Zinc finger protein GLI2 FORM GAMMA GLSK_HUMANISO O94925 Glutaminase kidney isoform FORM GAC mitochondrial precursor GPT_HUMANMAJOR Q9H3H5 UDP-N-acetylglucosamine-- ISOFORM dolichyl-phosphate N- GRB2_HUMANMAJOR P29354 Growth factor receptor-bound ISOFORM protein 2 HAIR_HUMANMAJOR O43593 Hairless protein ISOFORM HAIR_HUMANISO O43593 Hairless protein FORM SHORT HFE_HUMANMAJOR Q9HC68 Hereditary ISOFORM hemochromatosis protein precursor I17S_HUMANISO Q9NRM6 Interleukin-17B receptor FORM 2 precursor ICE2_HUMANISO P42575 Caspase-2 precursor FORM ICH-1S ICE8_HUMANISO Q9C0K4 Caspase-8 precursor FORM 7 ICEA_HUMANISO Q92851 Caspase-10 precursor FORM B ICEA_HUMANISO Q92851 Caspase-10 precursor FORM C ILF1_HUMANISO Q01167 Interleukin enhancer- FORM 2 binding factor 1 IRF7_HUMANISO Q92985 Interferon regulatory factor 7 FORM C IRL1_HUMANISO Q01638 Interleukin 1 receptor-like FORM C 1 precursor ITP1_HUMANMAJOR O14713 Integrin beta-1 binding ISOFORM protein 1 ITP1_HUMANISO O14713 Integrin beta-1 binding FORM 2 protein 1 KC11_HUMANIS Q9HCP0 Casein kinase I gamma 1 OFORM 1S isoform KLK2_HUMANIS P20151 Glandular kallikrein 2 OFORM 3 precursor KLKF_HUMANISO Q9H2R5 Kallikrein 15 precursor FORM 2 LEF1_HUMANISO Q9UJU2 Lymphoid enhancer FORM B binding factor 1 LFA3_HUMANISO P19256 Lymphocyte function- FORM SHORT associated antigen 3 precursor LIK1_HUMANISO P53667 LIM domain kinase 1 FORM 3 LSHR_HUMANMAJOR P22888 Lutropin- ISOFORM choriogonadotropic hormone receptor precursor LYST_HUMANMAJOR Q99698 Lysosomal trafficking ISOFORM regulator M2A2_HUMANISO P49641 Alpha-mannosidase IIx FORM SHORT MADI_HUMANISO O95405 Mothers against FORM 2 decapentaplegic homolog interacting protein MAP2_HUMAN P11137 Microtubule-associated MAJOR protein 2 ISOFORM MAP2_HUMANI P11137 Microtubule-associated SOFORM MAP2C protein 2 MAP4_HUMANI P27816 Microtubule-associated SOFORM 2 protein 4 MAX_HUMANISO P25912 Max protein FORM 3 MK11_HUMANISO Q15759 Mitogen-activated protein FORM BETA-2 kinase 11 MLH3_HUMANISO Q9UHC1 DNA mismatch repair FORM 2 protein Mlh3 MRP3_HUMANISO O15438 Canalicular multispecific FORM 3A organic anion transporter 2 MRP3_HUMANISO O15438 Canalicular multispecific FORM 3B organic anion transporter 2 MSRE_HUMANISO P21757 Macrophage scavenger FORM II receptor types I and II MTF2_HUMANMAJOR Q9Y483 Metal-response element- ISOFORM binding transcription factor 2 NK31_HUMANMAJOR Q99801 Homeobox protein Nkx-31 ISOFORM NXF5_HUMANMAJOR Q9H1B4 Nuclear RNA export factor 5 ISOFORM NXFS_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM B NXFS_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM C NXF5_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM D NXFS_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM E PHMX_HUMANISO Q96QS1 Phemx protein FORM 4 PHMX_HUMANISO Q96QS1 Phemx protein FORM 5 PML_HUMANISO P29590 Probable transcription FORM PML-3B factor PML PPE1_HUMANISO O14829 Serine/threonine protein FORM 2 phosphatase with EF- hands-1 PPT2_HUMANISO Q9UMR5 Palmitoyl-protein FORM 2 thioesterase 2 precursor PRD7_HUMANMAJOR Q9NQW5 PR-domain zinc finger ISOFORM protein 7 PSA7_HUMANISO O14818 Proteasome subunit alpha FORM 4 type 7 PSD4_HUMANISO P55036 26S proteasome non- FORM RPN10E ATPase regulatory subunit 4 PSN1_HUMANISO P49768 Presenilin 1 FORM I-374 PTPD_HUMANMAJOR P23468 Protein-tyrosine ISOFORM phosphatase delta precursor R51D_HUMANISO O94908 DNA repair protein FORM 2 RAD51 homolog 4 RBMS_HUMAN Q93062 RNA-binding protein with MAJOR multiple splicing ISOFORM RED1_HUMANMAJOR P78563 Double-stranded RNA- ISOFORM specific editase 1 RHD_HUMANMAJOR Q9UQ21 Blood group Rh ISOFORM RHD_HUMANISO Q9UQ21 Blood group Rh FORM 3 RYK_HUMANMAJOR P34925 Tyrosine-protein kinase ISOFORM RYK precursor RYK_HUMANIS P34925 Tyrosine-protein kinase OFORM 2 RYK precursor SCA1_ HUMANISO O15126 Secretory carrier-associated FORM 2 membrane protein 1 SEN7_HUMANMAJOR Q9BQF6 Sentrin-specific protease 7 ISOFORM SFR5_HUMANISO Q13243 Splicing factor FORM SRP40-2 arginine/serine-rich 5 SHX2_HUMANMAJOR O60902 Short stature homeobox ISOFORM protein 2 SNB2 HUMANISO Q13425 Beta-2-syntrophin FORM 2 SNXD_HUMANISO Q9Y5W8 Sorting nexin 13 FORM 2 SON_HUMANISO Q9UPY0 SON protein FORM C SON_HUMANISO Q9UPY0 SON protein FORM E SUR5_HUMANISO Q15528 Surfeit locus protein 5 FORM SURF5A T10B_HUMANMAJOR O14763 Tumor necrosis factor ISOFORM receptor superfamily member 10B precursor T10B HUMANISO O14763 Tumor necrosis factor FORM SHORT receptor superfamily member 10B precursor TM31_HUMANISO Q9BZY9 Tripartite motif protein 31 FORM BETA TNR6_HUMANISO P25445 Tumor necrosis factor FORM 2 receptor superfamily member 6 precursor TNR6_HUMANISO P25445 Tumor necrosis factor FORM 3 receptor superfamily member 6 precursor TNR6_HUMANISO P25445 Tumor necrosis factor FORM 4 receptor superfamily member 6 precursor TNR6_HUMANISO P25445 Tumor necrosis factor FORM 5 receptor superfamily member 6 precursor TPA_HUMANISO P00750 Tissue-type plasminogen FORM SHORT activator precursor TPO HUMANMAJOR P40225 Thrombopoietin precursor ISOFORM TR12_HUMANISO Q99831 Tumor necrosis factor FORM 12 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 3 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 4 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 5 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 6 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 7 receptor superfamily member 12 precursor U7I3_HUMANISO Q9BYM8 Ubiquitin conjugating FORM 2 enzyme 7 interacting protein 3 U713_HUMANISO Q9BYM8 Ubiquitin conjugating FORM 4 enzyme 7 interacting protein 3 USH3_HUMANISO P58418 Usher syndrome type 3 FORM B protein WS14_HUMANISO Q9NP71 Williams-Beuren syndrome FORM 5 chromosome region 14 protein XE7_HUMANISO Q02040 B-lymphocyte antigen FORM SHORT precursor Z236_HUMANISO Q9UL36 Zinc finger protein 236 FORM A ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 1 ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 2 ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 4 ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 5. 2. The method of claim 1 wherein the dataset of target putative protein isoform sequences comprises isoforms of Calpain-10, CLK1, CLK2, CLK3, and LARD/TNFRSF12. 3. A method for systematically characterizing putative protein isoforms as apparent targets of nonsense-mediated decay (NMD), the method comprising the following steps, each of which is performed with a suitably programmed computer: identifying a dataset of target putative protein isoform sequences from a curated protein sequence database for characterization; identifying corresponding gene intron-exon structures by mapping corresponding mRNA sequences of an mRNA sequence dataset to genomic sequences of a genomic DNA sequence dataset; screening the isoform dataset for a subset of isoforms encoded by transcripts comprising alternate splices which introduce a stop codon more than 50 nucleotides upstream of the final exon-exon splice junction; and classifying the subset isoforms as being encoded by transcripts comprising premature stop codons and as targets of NMD; and outputting from the computer a list of said isoforms that are apparent targets of NMD, wherein the dataset of target putative protein isoform sequences comprises a subset of the isoforms of Table 1: TABLE-US-00003 TABLE 1 Protein isoforms characterized as targets of NMD, ISOFORM NAME ACCESSION PROTEIN DESCRIPTION 3BP2_HUMANISO P78314 SH3 domain-binding protein 2 FORM SHORT 5H4_HUMANMAJOR Q13639 5-hydroxytryptamine 4 ISOFORM receptor A1A1_HUMANISO P05023 Sodium/potassium-transporting FORM SHORT ATPase alpha-1 chain precursor ABCD_HUMANISO Q9NSE7 Putative ATP-binding cassette FORM 2 transporter C13 ABCD_HUMANISO Q9NSE7 Putative ATP-binding cassette FORM 3 transporter C13 AD11_HUMANISO O75078 ADAM 11 precursor FORM SHORT AD12_HUMANMAJOR O43184 ADAM 12 precursor ISOFORM AD22_HUMANISO Q9POK1 ADAM 22 precursor FORM 2 AKP1_HUMANISO Q92667 A kinase anchor protein 1 FORM 2 mitochondrial precursor ANPB_HUMANISO P20594 Atrial natriuretic peptide FORM SHORT receptor B precursor AS13_HUMANMAJOR Q8WXK3 Ankyrin repeat and SOCS box ISOFORM containing protein 13 AS13_HUMANISO Q8WXK3 Ankyrin repeat and SOCS box FORM 2 containing protein 13 ATF3_HUMANISO P18847 Cyclic-AMP-dependent FORM 2 transcription factor ATF-3 ATR_HUMANMAJOR Q9H6X2 Anthrax toxin receptor ISOFORM precursor B3G7_HUMANISO Q9NY97 Beta-1 3-galactosyltransferase FORM 2 7 BC12_HUMANISO Q9HB09 Bcl-2 related proline-rich FORM 2 protein BMP1_HUMANISO P13497 Bone morphogenetic protein 1 FORM BMP1-4 precursor BMP1_HUMANISO P13497 Bone morphogenetic protein 1 FORM BMP1-5 precursor BMP1_HUMANISO P13497 Bone morphogenetic protein 1 FORM BMP1-6 precursor C343_HUMANISO Q9HB55 Cytochrome P450 3A43 FORM 4 CA34_HUMANMAJOR Q01955 Collagen alpha 3 ISOFORM CA34_HUMANISO Q01955 Collagen alpha 3 FORM 3 CAL0_HUMANISO P01258 Calcitonin precursor [Contains: FORM 2 Calcitonin; Katacalcin CANA_HUMANISO Q9HC93 Calpain 10 FORM B CANA_HUMANISO Q9HC93 Calpain 10 FORM D CANA_HUMANISO Q9HC93 Calpain 10 FORM E CANA_HUMANISO Q9HC93 Calpain 10 FORM F CBS_HUMANMAJOR P35520 Cystathionine beta-synthase ISOFORM CD38_HUMANISO P28907 ADP-ribosyl cyclase 1 FORM 2 CD47_HUMANISO Q08722 Leukocyte surface antigen FORM OA3-305 CD47 precursor CFLA_HUMANISO O43618 CASP8 and FADD-like FORM 9 apoptosis regulator precursor CHRD_HUMANISO Q9P0Z5 Chordin precursor FORM 3 CHRD_HUMANISO Q9P0Z5 Chordin precursor FORM 4 CIQ2_HUMANISO O43526 Potassium voltage-gated FORM 3 channel subfamily KQT member 2 CIW4_HUMANISO Q9NYG8 Potassium channel subfamily FORM 2 K member 4 CLK1_HUMANISO P49759 Protein kinase CLK1 FORM SHORT CLK2_HUMANISO P49760 Protein kinase CLK2 FORM SHORT CLK3_HUMANISO P49761 Protein kinase CLK3 FORM 2 CML1_HUMANMAJOR Q99788 Chemokine receptor-like 1 ISOFORM COG4_HUMANISO Q9H9E3 Conserved oilgomeric Golgi FORM 2 complex component 4 COLQ_HUMANISO Q9UP88 Acetylcholinesterase FORM VII collagenic tail peptide precursor CPXM_HUMANISO Q96SM3 Potential carboxypeptidase X FORM 2 precursor CRN1_HUMANISO Q9NYD8 Crooked neck-like protein 1 FORM 4 CRN1_HUMANISO Q9NYD8 Crooked neck-like protein 1 FORM 5 CT24_HUMANISO Q9BUV8 Protein C20orf24 FORM 4 CTGF_HUMANMAJOR P29279 Connective tissue growth ISOFORM factor precursor CU07_HUMANISO P57077 Protein C21orf7 FORM B CU07_HUMANISO P57077 Protein C21orf7 FORM C CU18_HUMANISO Q9NVD3 Protein C21orf18 FORM B CU63_HUMANISO P58658 Protein C21orf63 precursor FORM B CU80_HUMANISO Q9Y2G5 Protein C21orf80 FORM B CYB5_HUMANISO P00167 Cytochrome b5 FORM 2 DACA_HUMANISO Q9BYJ9 Dermatomyositis associated FORM 2 with cancer putative autoantigen-1 DFFB_HUMANISO O76075 DNA fragmentation factor 40 FORM BETA kDa subunit DFFB_HUMANISO O76075 DNA fragmentation factor 40 FORM DELTA kDa subunit DFFB_HUMANISO O76075 DNA fragmentation factor 40 FORM GAMMA kDa subunit DJB2_HUMANMAJOR P25686 DnaJ homolog subfamily B ISOFORM member 2 DJB2_HUMANISO P25686 DnaJ homolog subfamily B FORM 3 member 2 DONS_HUMANISO Q9NYP3 Downstream of son gene FORM 2 protein DONS_HUMANIS Q9NYP3 Downstream of son gene OFORM 3 protein DPP3_HUMANISO Q9NY33 Dipeptidyl-peptidase III FORM 2 DSCA_HUMANISO O60469 Down syndrome cell adhesion FORM SHORT molecule precursor DTNB_HUMANISO O60941 Dystrobrevin beta FORM 3 EPA3_HUMANMAJOR P29320 Ephrin type-A receptor 3 ISOFORM precursor ERAL_HUMANISO O75616 GTP-binding protein era FORM HERA-B homolog ESR2_HUMANISO Q9UHD3 Estrogen receptor beta FORM 3 F263_HUMANMAJOR Q16875 6-phosphofructo-2- ISOFORM kinase/fructose-2 6- biphosphatase 3 FAFY_HUMANISO O00507 Probable ubiquitin carboxyl- FORM SHORT terminal hydrolase FAF-Y FCAR_HUMANISO P24071 Immunoglobulin alpha Fc FORM B-DELTA- receptor precursor S2 FCE2_HUMANMAJOR P06734 Low affinity immunoglobulin ISOFORM epsilon FC receptor FTCD_HUMANISO O95954 Formimidoyltransferase- FORM E cyclodeaminase FUT8_HUMANISO Q9BYC5 Alpha-(1,6)-fucosyltransferase FORM 2 FXM1_HUMANISO Q08050 Forkhead box protein M1 FORM 2 G72_HUMANMAJOR P59103 Protein G72 ISOFORM G72_HUMANISO P59103 Protein G72 FORM 2 G8_HUMANMAJOR Q9UBA6 G8 protein ISOFORM GBR1_HUMANISO Q9UBS5 Gamma-aminobutyric acid FORM 1E type B receptor subunit 1 precursor GCFC_HUMANISO Q9Y5B6 GC-rich sequence DNA- FORM D binding factor homolog GCP2_HUMANISO Q9BSJ2 Gamma-tubulin complex FORM 2 component 2 GDNR_HUMANISO P56159 GDNF receptor alpha FORM 2 precursor GLI2_HUMANMAJOR P10070 Zinc finger protein GLI2 ISOFORM GLI2_HUMANISO P10070 Zinc finger protein GLI2 FORM BETA GLI2_HUMANISO P10070 Zinc finger protein GLI2 FORM DELTA GLI2_HUMANISO P10070 Zinc finger protein GLI2 FORM GAMMA GLSK_HUMANISO O94925 Glutaminase kidney isoform FORM GAC mitochondrial precursor GPT_HUMANMAJOR Q9H3H5 UDP-N-acetylglucosamine-- ISOFORM dolichyl-phosphate N- GRB2_HUMANMAJOR P29354 Growth factor receptor-bound ISOFORM protein 2 HAIR_HUMANMAJOR O43593 Hairless protein ISOFORM HAIR_HUMANISO O43593 Hairless protein FORM SHORT HFE_HUMANMAJOR Q9HC68 Hereditary ISOFORM hemochromatosis protein precursor I17S_HUMANISO Q9NRM6 Interleukin-17B receptor FORM 2 precursor ICE2_HUMANISO P42575 Caspase-2 precursor FORM ICH-1S ICE8_HUMANISO Q9C0K4 Caspase-8 precursor FORM 7 ICEA_HUMANISO Q92851 Caspase-10 precursor FORM B ICEA_HUMANISO Q92851 Caspase-10 precursor FORM C ILF1_HUMANISO Q01167 Interleukin enhancer- FORM 2 binding factor 1 IRF7_HUMANISO Q92985 Interferon regulatory factor 7 FORM C IRL1_HUMANISO Q01638 Interleukin 1 receptor-like FORM C 1 precursor ITP1_HUMANMAJOR O14713 Integrin beta-1 binding ISOFORM protein 1 ITP1_HUMANISO O14713 Integrin beta-1 binding FORM 2 protein 1 KC11_HUMANIS Q9HCP0 Casein kinase I gamma 1 OFORM 1S isoform KLK2_HUMANIS P20151 Glandular kallikrein 2 OFORM 3 precursor KLKF_HUMANISO Q9H2R5 Kallikrein 15 precursor FORM 2 LEF1_HUMANISO Q9UJU2 Lymphoid enhancer FORM B binding factor 1 LFA3_HUMANISO P19256 Lymphocyte function- FORM SHORT associated antigen 3 precursor LIK1_HUMANISO P53667 LIM domain kinase 1 FORM 3 LSHR_HUMANMAJOR P22888 Lutropin- ISOFORM choriogonadotropic hormone receptor precursor LYST_HUMANMAJOR Q99698 Lysosomal trafficking ISOFORM regulator M2A2_HUMANISO P49641 Alpha-mannosidase IIx FORM SHORT MADI_HUMANISO O95405 Mothers against FORM 2 decapentaplegic homolog interacting protein MAP2_HUMAN P11137 Microtubule-associated MAJOR protein 2 ISOFORM MAP2_HUMANI P11137 Microtubule-associated SOFORM MAP2C protein 2 MAP4_HUMANI P27816 Microtubule-associated SOFORM 2 protein 4 MAX_HUMANISO P25912 Max protein FORM 3 MK11_HUMANISO Q15759 Mitogen-activated protein FORM BETA-2 kinase 11 MLH3_HUMANISO Q9UHC1 DNA mismatch repair FORM 2 protein Mlh3 MRP3_HUMANISO O15438 Canalicular multispecific FORM 3A organic anion transporter 2 MRP3_HUMANISO O15438 Canalicular multispecific FORM 3B organic anion transporter 2 MSRE_HUMANISO P21757 Macrophage scavenger FORM II receptor types I and II MTF2_HUMANMAJOR Q9Y483 Metal-response element- ISOFORM binding transcription factor 2 NK31_HUMANMAJOR Q99801 Homeobox protein Nkx-31 ISOFORM NXF5_HUMANMAJOR Q9H1B4 Nuclear RNA export factor 5 ISOFORM NXFS_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM B NXFS_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM C NXF5_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM D NXFS_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM E PHMX_HUMANISO Q96QS1 Phemx protein FORM 4 PHMX_HUMANISO Q96QS1 Phemx protein FORM 5 PML_HUMANISO P29590 Probable transcription FORM PML-3B factor PML PPE1_HUMANISO O14829 Serine/threonine protein FORM 2 phosphatase with EF- hands-1 PPT2_HUMANISO Q9UMR5 Palmitoyl-protein FORM 2 thioesterase 2 precursor PRD7_HUMANMAJOR Q9NQW5 PR-domain zinc finger ISOFORM protein 7 PSA7_HUMANISO O14818 Proteasome subunit alpha FORM 4 type 7 PSD4_HUMANISO P55036 26S proteasome non- FORM RPN10E ATPase regulatory subunit 4 PSN1_HUMANISO P49768 Presenilin 1 FORM I-374 PTPD_HUMANMAJOR P23468 Protein-tyrosine ISOFORM phosphatase delta precursor R51D_HUMANISO O94908 DNA repair protein FORM 2 RAD51 homolog 4 RBMS_HUMAN Q93062 RNA-binding protein with MAJOR multiple splicing ISOFORM RED1_HUMANMAJOR P78563 Double-stranded RNA- ISOFORM specific editase 1 RHD_HUMANMAJOR Q9UQ21 Blood group Rh ISOFORM RHD_HUMANISO Q9UQ21 Blood group Rh FORM 3 RYK_HUMANMAJOR P34925 Tyrosine-protein kinase ISOFORM RYK precursor RYK_HUMANIS P34925 Tyrosine-protein kinase OFORM 2 RYK precursor SCA1_ HUMANISO O15126 Secretory carrier-associated FORM 2 membrane protein 1 SEN7_HUMANMAJOR Q9BQF6 Sentrin-specific protease 7 ISOFORM SFR5_HUMANISO Q13243 Splicing factor FORM SRP40-2 arginine/serine-rich 5 SHX2_HUMANMAJOR O60902 Short stature homeobox ISOFORM protein 2 SNB2 HUMANISO Q13425 Beta-2-syntrophin FORM 2 SNXD_HUMANISO Q9Y5W8 Sorting nexin 13 FORM 2 SON_HUMANISO Q9UPY0 SON protein FORM C SON_HUMANISO Q9UPY0 SON protein FORM E SUR5_HUMANISO Q15528 Surfeit locus protein 5 FORM SURF5A T10B_HUMANMAJOR O14763 Tumor necrosis factor ISOFORM receptor superfamily member 10B precursor T10B HUMANISO O14763 Tumor necrosis factor FORM SHORT receptor superfamily member 10B precursor TM31_HUMANISO Q9BZY9 Tripartite motif protein 31 FORM BETA TNR6_HUMANISO P25445 Tumor necrosis factor FORM 2 receptor superfamily member 6 precursor TNR6_HUMANISO P25445 Tumor necrosis factor FORM 3 receptor superfamily member 6 precursor TNR6_HUMANISO P25445 Tumor necrosis factor FORM 4 receptor superfamily member 6 precursor TNR6_HUMANISO P25445 Tumor necrosis factor FORM 5 receptor superfamily member 6 precursor TPA_HUMANISO P00750 Tissue-type plasminogen FORM SHORT activator precursor TPO HUMANMAJOR P40225 Thrombopoietin precursor ISOFORM TR12_HUMANISO Q99831 Tumor necrosis factor FORM 12 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 3 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 4 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 5 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 6 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 7 receptor superfamily member 12 precursor U7I3_HUMANISO Q9BYM8 Ubiquitin conjugating FORM 2 enzyme 7 interacting protein 3 U713_HUMANISO Q9BYM8 Ubiquitin conjugating FORM 4 enzyme 7 interacting protein 3 USH3_HUMANISO P58418 Usher syndrome type 3 FORM B protein WS14_HUMANISO Q9NP71 Williams-Beuren syndrome FORM 5 chromosome region 14 protein XE7_HUMANISO Q02040 B-lymphocyte antigen FORM SHORT precursor Z236_HUMANISO Q9UL36 Zinc finger protein 236 FORM A ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 1 ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 2 ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 4 ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 5. 4. The method of claim 3 wherein the dataset of target putative protein isoform sequences comprises isoforms of Calpain-10, CLK1, CLK2, CLK3, and LARD/TNFRSF12. 5. A computer program product, comprising a computer usable medium having a computer readable program code embodied therein, said computer readable program code adapted to be executed to implement a method for systematically characterizing putative protein isoforms as apparent targets of nonsense-mediated decay (NMD) and for generating and outputting a list of said isoforms, the method comprising the following steps: identifying a dataset of target putative protein isoform sequences from a curated protein sequence database for characterization; identifying from an mRNA dataset corresponding mRNA sequences representing transcripts encoding the protein isoforms, wherein each of the transcripts comprises a termination codon and a final intron; determining corresponding gene intron-exon structures by mapping the mRNA sequences to corresponding genomic sequences; determining if the transcripts are apparent targets of NMD by comparing the position of the termination codon to the position of the final intron, wherein if the termination codon of the transcript is more than 50 nucleotides upstream of the final intron position, then the transcript is an apparent target of NMD; and outputting from the computer a list of said isoforms that are apparent targets of NMD, wherein the dataset of target putative protein isoform sequences comprises a subset of the isoforms of Table 1: TABLE-US-00004 TABLE 1 Protein isoforms characterized as targets of NMD, ISOFORM NAME ACCESSION PROTEIN DESCRIPTION 3BP2_HUMANISO P78314 SH3 domain-binding protein 2 FORM SHORT 5H4_HUMANMAJOR Q13639 5-hydroxytryptamine 4 ISOFORM receptor A1A1_HUMANISO P05023 Sodium/potassium-transporting FORM SHORT ATPase alpha-1 chain precursor ABCD_HUMANISO Q9NSE7 Putative ATP-binding cassette FORM 2 transporter C13 ABCD_HUMANISO Q9NSE7 Putative ATP-binding cassette FORM 3 transporter C13 AD11_HUMANISO O75078 ADAM 11 precursor FORM SHORT AD12_HUMANMAJOR O43184 ADAM 12 precursor ISOFORM AD22_HUMANISO Q9POK1 ADAM 22 precursor FORM 2 AKP1_HUMANISO Q92667 A kinase anchor protein 1 FORM 2 mitochondrial precursor ANPB_HUMANISO P20594 Atrial natriuretic peptide FORM SHORT receptor B precursor AS13_HUMANMAJOR Q8WXK3 Ankyrin repeat and SOCS box ISOFORM containing protein 13 AS13_HUMANISO Q8WXK3 Ankyrin repeat and SOCS box FORM 2 containing protein 13 ATF3_HUMANISO P18847 Cyclic-AMP-dependent FORM 2 transcription factor ATF-3 ATR_HUMANMAJOR Q9H6X2 Anthrax toxin receptor ISOFORM precursor B3G7_HUMANISO Q9NY97 Beta-1 3-galactosyltransferase FORM 2 7 BC12_HUMANISO Q9HB09 Bcl-2 related proline-rich FORM 2 protein BMP1_HUMANISO P13497 Bone morphogenetic protein 1 FORM BMP1-4 precursor BMP1_HUMANISO P13497 Bone morphogenetic protein 1 FORM BMP1-5 precursor BMP1_HUMANISO P13497 Bone morphogenetic protein 1 FORM BMP1-6 precursor C343_HUMANISO Q9HB55 Cytochrome P450 3A43 FORM 4 CA34_HUMANMAJOR Q01955 Collagen alpha 3 ISOFORM CA34_HUMANISO Q01955 Collagen alpha 3 FORM 3 CAL0_HUMANISO P01258 Calcitonin precursor [Contains: FORM 2 Calcitonin; Katacalcin CANA_HUMANISO Q9HC93 Calpain 10 FORM B CANA_HUMANISO Q9HC93 Calpain 10 FORM D CANA_HUMANISO Q9HC93 Calpain 10 FORM E CANA_HUMANISO Q9HC93 Calpain 10 FORM F CBS_HUMANMAJOR P35520 Cystathionine beta-synthase ISOFORM CD38_HUMANISO P28907 ADP-ribosyl cyclase 1 FORM 2 CD47_HUMANISO Q08722 Leukocyte surface antigen FORM OA3-305 CD47 precursor CFLA_HUMANISO O43618 CASP8 and FADD-like FORM 9 apoptosis regulator precursor CHRD_HUMANISO Q9P0Z5 Chordin precursor FORM 3 CHRD_HUMANISO Q9P0Z5 Chordin precursor FORM 4 CIQ2_HUMANISO O43526 Potassium voltage-gated FORM 3 channel subfamily KQT member 2 CIW4_HUMANISO Q9NYG8 Potassium channel subfamily FORM 2 K member 4 CLK1_HUMANISO P49759 Protein kinase CLK1 FORM SHORT CLK2_HUMANISO P49760 Protein kinase CLK2 FORM SHORT CLK3_HUMANISO P49761 Protein kinase CLK3 FORM 2 CML1_HUMANMAJOR Q99788 Chemokine receptor-like 1 ISOFORM COG4_HUMANISO Q9H9E3 Conserved oilgomeric Golgi FORM 2 complex component 4 COLQ_HUMANISO Q9UP88 Acetylcholinesterase FORM VII collagenic tail peptide precursor CPXM_HUMANISO Q96SM3 Potential carboxypeptidase X FORM 2 precursor CRN1_HUMANISO Q9NYD8 Crooked neck-like protein 1 FORM 4 CRN1_HUMANISO Q9NYD8 Crooked neck-like protein 1 FORM 5 CT24_HUMANISO Q9BUV8 Protein C20orf24 FORM 4 CTGF_HUMANMAJOR P29279 Connective tissue growth ISOFORM factor precursor CU07_HUMANISO P57077 Protein C21orf7 FORM B CU07_HUMANISO P57077 Protein C21orf7 FORM C CU18_HUMANISO Q9NVD3 Protein C21orf18 FORM B CU63_HUMANISO P58658 Protein C21orf63 precursor FORM B CU80_HUMANISO Q9Y2G5 Protein C21orf80 FORM B CYB5_HUMANISO P00167 Cytochrome b5 FORM 2 DACA_HUMANISO Q9BYJ9 Dermatomyositis associated FORM 2 with cancer putative autoantigen-1 DFFB_HUMANISO O76075 DNA fragmentation factor 40 FORM BETA kDa subunit DFFB_HUMANISO O76075 DNA fragmentation factor 40 FORM DELTA kDa subunit DFFB_HUMANISO O76075 DNA fragmentation factor 40 FORM GAMMA kDa subunit DJB2_HUMANMAJOR P25686 DnaJ homolog subfamily B ISOFORM member 2 DJB2_HUMANISO P25686 DnaJ homolog subfamily B FORM 3 member 2 DONS_HUMANISO Q9NYP3 Downstream of son gene FORM 2 protein DONS_HUMANIS Q9NYP3 Downstream of son gene OFORM 3 protein DPP3_HUMANISO Q9NY33 Dipeptidyl-peptidase III FORM 2 DSCA_HUMANISO O60469 Down syndrome cell adhesion FORM SHORT molecule precursor DTNB_HUMANISO O60941 Dystrobrevin beta FORM 3 EPA3_HUMANMAJOR P29320 Ephrin type-A receptor 3 ISOFORM precursor ERAL_HUMANISO O75616 GTP-binding protein era FORM HERA-B homolog ESR2_HUMANISO Q9UHD3 Estrogen receptor beta FORM 3 F263_HUMANMAJOR Q16875 6-phosphofructo-2- ISOFORM kinase/fructose-2 6- biphosphatase 3 FAFY_HUMANISO O00507 Probable ubiquitin carboxyl- FORM SHORT terminal hydrolase FAF-Y FCAR_HUMANISO P24071 Immunoglobulin alpha Fc FORM B-DELTA- receptor precursor S2 FCE2_HUMANMAJOR P06734 Low affinity immunoglobulin ISOFORM epsilon FC receptor FTCD_HUMANISO O95954 Formimidoyltransferase- FORM E cyclodeaminase FUT8_HUMANISO Q9BYC5 Alpha-(1,6)-fucosyltransferase FORM 2 FXM1_HUMANISO Q08050 Forkhead box protein M1 FORM 2 G72_HUMANMAJOR P59103 Protein G72 ISOFORM G72_HUMANISO P59103 Protein G72 FORM 2 G8_HUMANMAJOR Q9UBA6 G8 protein ISOFORM GBR1_HUMANISO Q9UBS5 Gamma-aminobutyric acid FORM 1E type B receptor subunit 1 precursor GCFC_HUMANISO Q9Y5B6 GC-rich sequence DNA- FORM D binding factor homolog GCP2_HUMANISO Q9BSJ2 Gamma-tubulin complex FORM 2 component 2 GDNR_HUMANISO P56159 GDNF receptor alpha FORM 2 precursor GLI2_HUMANMAJOR P10070 Zinc finger protein GLI2 ISOFORM GLI2_HUMANISO P10070 Zinc finger protein GLI2 FORM BETA GLI2_HUMANISO P10070 Zinc finger protein GLI2 FORM DELTA GLI2_HUMANISO P10070 Zinc finger protein GLI2 FORM GAMMA GLSK_HUMANISO O94925 Glutaminase kidney isoform FORM GAC mitochondrial precursor GPT_HUMANMAJOR Q9H3H5 UDP-N-acetylglucosamine-- ISOFORM dolichyl-phosphate N- GRB2_HUMANMAJOR P29354 Growth factor receptor-bound ISOFORM protein 2 HAIR_HUMANMAJOR O43593 Hairless protein ISOFORM HAIR_HUMANISO O43593 Hairless protein FORM SHORT HFE_HUMANMAJOR Q9HC68 Hereditary ISOFORM hemochromatosis protein precursor I17S_HUMANISO Q9NRM6 Interleukin-17B receptor FORM 2 precursor ICE2_HUMANISO P42575 Caspase-2 precursor FORM ICH-1S ICE8_HUMANISO Q9C0K4 Caspase-8 precursor FORM 7 ICEA_HUMANISO Q92851 Caspase-10 precursor FORM B ICEA_HUMANISO Q92851 Caspase-10 precursor FORM C ILF1_HUMANISO Q01167 Interleukin enhancer- FORM 2 binding factor 1 IRF7_HUMANISO Q92985 Interferon regulatory factor 7 FORM C IRL1_HUMANISO Q01638 Interleukin 1 receptor-like FORM C 1 precursor ITP1_HUMANMAJOR O14713 Integrin beta-1 binding ISOFORM protein 1 ITP1_HUMANISO O14713 Integrin beta-1 binding FORM 2 protein 1 KC11_HUMANIS Q9HCP0 Casein kinase I gamma 1 OFORM 1S isoform KLK2_HUMANIS P20151 Glandular kallikrein 2 OFORM 3 precursor KLKF_HUMANISO Q9H2R5 Kallikrein 15 precursor FORM 2 LEF1_HUMANISO Q9UJU2 Lymphoid enhancer FORM B binding factor 1 LFA3_HUMANISO P19256 Lymphocyte function- FORM SHORT associated antigen 3 precursor LIK1_HUMANISO P53667 LIM domain kinase 1 FORM 3 LSHR_HUMANMAJOR P22888 Lutropin- ISOFORM choriogonadotropic hormone receptor precursor LYST_HUMANMAJOR Q99698 Lysosomal trafficking ISOFORM regulator M2A2_HUMANISO P49641 Alpha-mannosidase IIx FORM SHORT MADI_HUMANISO O95405 Mothers against FORM 2 decapentaplegic homolog interacting protein MAP2_HUMAN P11137 Microtubule-associated MAJOR protein 2 ISOFORM MAP2_HUMANI P11137 Microtubule-associated SOFORM MAP2C protein 2 MAP4_HUMANI P27816 Microtubule-associated SOFORM 2 protein 4 MAX_HUMANISO P25912 Max protein FORM 3 MK11_HUMANISO Q15759 Mitogen-activated protein FORM BETA-2 kinase 11 MLH3_HUMANISO Q9UHC1 DNA mismatch repair FORM 2 protein Mlh3 MRP3_HUMANISO O15438 Canalicular multispecific FORM 3A organic anion transporter 2 MRP3_HUMANISO O15438 Canalicular multispecific FORM 3B organic anion transporter 2 MSRE_HUMANISO P21757 Macrophage scavenger FORM II receptor types I and II MTF2_HUMANMAJOR Q9Y483 Metal-response element- ISOFORM binding transcription factor 2 NK31_HUMANMAJOR Q99801 Homeobox protein Nkx-31 ISOFORM NXF5_HUMANMAJOR Q9H1B4 Nuclear RNA export factor 5 ISOFORM NXFS_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM B NXFS_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM C NXF5_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM D NXFS_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM E PHMX_HUMANISO Q96QS1 Phemx protein FORM 4 PHMX_HUMANISO Q96QS1 Phemx protein FORM 5 PML_HUMANISO P29590 Probable transcription FORM PML-3B factor PML PPE1_HUMANISO O14829 Serine/threonine protein FORM 2 phosphatase with EF- hands-1 PPT2_HUMANISO Q9UMR5 Palmitoyl-protein FORM 2 thioesterase 2 precursor PRD7_HUMANMAJOR Q9NQW5 PR-domain zinc finger ISOFORM protein 7 PSA7_HUMANISO O14818 Proteasome subunit alpha FORM 4 type 7 PSD4_HUMANISO P55036 26S proteasome non- FORM RPN10E ATPase regulatory subunit 4 PSN1_HUMANISO P49768 Presenilin 1 FORM I-374 PTPD_HUMANMAJOR P23468 Protein-tyrosine ISOFORM phosphatase delta precursor R51D_HUMANISO O94908 DNA repair protein FORM 2 RAD51 homolog 4 RBMS_HUMAN Q93062 RNA-binding protein with MAJOR multiple splicing ISOFORM RED1_HUMANMAJOR P78563 Double-stranded RNA- ISOFORM specific editase 1 RHD_HUMANMAJOR Q9UQ21 Blood group Rh ISOFORM RHD_HUMANISO Q9UQ21 Blood group Rh FORM 3 RYK_HUMANMAJOR P34925 Tyrosine-protein kinase ISOFORM RYK precursor RYK_HUMANIS P34925 Tyrosine-protein kinase OFORM 2 RYK precursor SCA1_ HUMANISO O15126 Secretory carrier-associated FORM 2 membrane protein 1 SEN7_HUMANMAJOR Q9BQF6 Sentrin-specific protease 7 ISOFORM SFR5_HUMANISO Q13243 Splicing factor FORM SRP40-2 arginine/serine-rich 5 SHX2_HUMANMAJOR O60902 Short stature homeobox ISOFORM protein 2 SNB2 HUMANISO Q13425 Beta-2-syntrophin FORM 2 SNXD_HUMANISO Q9Y5W8 Sorting nexin 13 FORM 2 SON_HUMANISO Q9UPY0 SON protein FORM C SON_HUMANISO Q9UPY0 SON protein FORM E SUR5_HUMANISO Q15528 Surfeit locus protein 5 FORM SURF5A T10B_HUMANMAJOR O14763 Tumor necrosis factor ISOFORM receptor superfamily member 10B precursor T10B HUMANISO O14763 Tumor necrosis factor FORM SHORT receptor superfamily member 10B precursor TM31_HUMANISO Q9BZY9 Tripartite motif protein 31 FORM BETA TNR6_HUMANISO P25445 Tumor necrosis factor FORM 2 receptor superfamily member 6 precursor TNR6_HUMANISO P25445 Tumor necrosis factor FORM 3 receptor superfamily member 6 precursor TNR6_HUMANISO P25445 Tumor necrosis factor FORM 4 receptor superfamily member 6 precursor TNR6_HUMANISO P25445 Tumor necrosis factor FORM 5 receptor superfamily member 6 precursor TPA_HUMANISO P00750 Tissue-type plasminogen FORM SHORT activator precursor TPO HUMANMAJOR P40225 Thrombopoietin precursor ISOFORM TR12_HUMANISO Q99831 Tumor necrosis factor FORM 12 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 3 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 4 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 5 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 6 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 7 receptor superfamily member 12 precursor U7I3_HUMANISO Q9BYM8 Ubiquitin conjugating FORM 2 enzyme 7 interacting protein 3 U713_HUMANISO Q9BYM8 Ubiquitin conjugating FORM 4 enzyme 7 interacting protein 3 USH3_HUMANISO P58418 Usher syndrome type 3 FORM B protein WS14_HUMANISO Q9NP71 Williams-Beuren syndrome FORM 5 chromosome region 14 protein XE7_HUMANISO Q02040 B-lymphocyte antigen FORM SHORT precursor Z236_HUMANISO Q9UL36 Zinc finger protein 236 FORM A ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 1 ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 2 ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 4 ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 5. 6. The product of claim 5 wherein the dataset of target putative protein isoform sequences comprises isoforms of Calpain-10, CLK1, CLK2, CLK3, and LARD/TNFRSF12. 7. A computer program product, comprising a computer usable medium having a computer readable program code embodied therein, said computer readable program code adapted to be executed to implement a method for systematically characterizing putative protein isoforms as apparent targets of nonsense-mediated decay (NMD) and for generating and outputting a list of said isoforms, the method comprising the following steps: identifying a dataset of target putative protein isoform sequences from a curated protein sequence database for characterization; identifying corresponding gene intron-exon structures by mapping corresponding mRNA sequences of an mRNA sequence dataset to genomic sequences of a genomic DNA sequence dataset; screening the isoform dataset for a subset of isoforms encoded by transcripts comprising alternate splices which introduce a stop codon more than 50 nucleotides upstream of the final exon-exon splice junction; and classifying the subset isoforms as being encoded by transcripts comprising premature stop codons and as targets of NMD; and outputting from the computer a list of said isoforms that are apparent targets of NMD, wherein the dataset of target putative protein isoform sequences comprises a subset of the isoforms of Table 1: TABLE-US-00005 TABLE 1 Protein isoforms characterized as targets of NMD, ISOFORM NAME ACCESSION PROTEIN DESCRIPTION 3BP2_HUMANISO P78314 SH3 domain-binding protein 2 FORM SHORT 5H4_HUMANMAJOR Q13639 5-hydroxytryptamine 4 ISOFORM receptor A1A1_HUMANISO P05023 Sodium/potassium-transporting FORM SHORT ATPase alpha-1 chain precursor ABCD_HUMANISO Q9NSE7 Putative ATP-binding cassette FORM 2 transporter C13 ABCD_HUMANISO Q9NSE7 Putative ATP-binding cassette FORM 3 transporter C13 AD11_HUMANISO O75078 ADAM 11 precursor FORM SHORT AD12_HUMANMAJOR O43184 ADAM 12 precursor ISOFORM AD22_HUMANISO Q9POK1 ADAM 22 precursor FORM 2 AKP1_HUMANISO Q92667 A kinase anchor protein 1 FORM 2 mitochondrial precursor ANPB_HUMANISO P20594 Atrial natriuretic peptide FORM SHORT receptor B precursor AS13_HUMANMAJOR Q8WXK3 Ankyrin repeat and SOCS box ISOFORM containing protein 13 AS13_HUMANISO Q8WXK3 Ankyrin repeat and SOCS box FORM 2 containing protein 13 ATF3_HUMANISO P18847 Cyclic-AMP-dependent FORM 2 transcription factor ATF-3 ATR_HUMANMAJOR Q9H6X2 Anthrax toxin receptor ISOFORM precursor B3G7_HUMANISO Q9NY97 Beta-1 3-galactosyltransferase FORM 2 7 BC12_HUMANISO Q9HB09 Bcl-2 related proline-rich FORM 2 protein BMP1_HUMANISO P13497 Bone morphogenetic protein 1 FORM BMP1-4 precursor BMP1_HUMANISO P13497 Bone morphogenetic protein 1 FORM BMP1-5 precursor BMP1_HUMANISO P13497 Bone morphogenetic protein 1 FORM BMP1-6 precursor C343_HUMANISO Q9HB55 Cytochrome P450 3A43 FORM 4 CA34_HUMANMAJOR Q01955 Collagen alpha 3 ISOFORM CA34_HUMANISO Q01955 Collagen alpha 3 FORM 3 CAL0_HUMANISO P01258 Calcitonin precursor [Contains: FORM 2 Calcitonin; Katacalcin CANA_HUMANISO Q9HC93 Calpain 10 FORM B CANA_HUMANISO Q9HC93 Calpain 10 FORM D CANA_HUMANISO Q9HC93 Calpain 10 FORM E CANA_HUMANISO Q9HC93 Calpain 10 FORM F CBS_HUMANMAJOR P35520 Cystathionine beta-synthase ISOFORM CD38_HUMANISO P28907 ADP-ribosyl cyclase 1 FORM 2 CD47_HUMANISO Q08722 Leukocyte surface antigen FORM OA3-305 CD47 precursor CFLA_HUMANISO O43618 CASP8 and FADD-like FORM 9 apoptosis regulator precursor CHRD_HUMANISO Q9P0Z5 Chordin precursor FORM 3 CHRD_HUMANISO Q9P0Z5 Chordin precursor FORM 4 CIQ2_HUMANISO O43526 Potassium voltage-gated FORM 3 channel subfamily KQT member 2 CIW4_HUMANISO Q9NYG8 Potassium channel subfamily FORM 2 K member 4 CLK1_HUMANISO P49759 Protein kinase CLK1 FORM SHORT CLK2_HUMANISO P49760 Protein kinase CLK2 FORM SHORT CLK3_HUMANISO P49761 Protein kinase CLK3 FORM 2 CML1_HUMANMAJOR Q99788 Chemokine receptor-like 1 ISOFORM COG4_HUMANISO Q9H9E3 Conserved oilgomeric Golgi FORM 2 complex component 4 COLQ_HUMANISO Q9UP88 Acetylcholinesterase FORM VII collagenic tail peptide precursor CPXM_HUMANISO Q96SM3 Potential carboxypeptidase X FORM 2 precursor CRN1_HUMANISO Q9NYD8 Crooked neck-like protein 1 FORM 4 CRN1_HUMANISO Q9NYD8 Crooked neck-like protein 1 FORM 5 CT24_HUMANISO Q9BUV8 Protein C20orf24 FORM 4 CTGF_HUMANMAJOR P29279 Connective tissue growth ISOFORM factor precursor CU07_HUMANISO P57077 Protein C21orf7 FORM B CU07_HUMANISO P57077 Protein C21orf7 FORM C CU18_HUMANISO Q9NVD3 Protein C21orf18 FORM B CU63_HUMANISO P58658 Protein C21orf63 precursor FORM B CU80_HUMANISO Q9Y2G5 Protein C21orf80 FORM B CYB5_HUMANISO P00167 Cytochrome b5 FORM 2 DACA_HUMANISO Q9BYJ9 Dermatomyositis associated FORM 2 with cancer putative autoantigen-1 DFFB_HUMANISO O76075 DNA fragmentation factor 40 FORM BETA kDa subunit DFFB_HUMANISO O76075 DNA fragmentation factor 40 FORM DELTA kDa subunit DFFB_HUMANISO O76075 DNA fragmentation factor 40 FORM GAMMA kDa subunit DJB2_HUMANMAJOR P25686 DnaJ homolog subfamily B ISOFORM member 2 DJB2_HUMANISO P25686 DnaJ homolog subfamily B FORM 3 member 2 DONS_HUMANISO Q9NYP3 Downstream of son gene FORM 2 protein DONS_HUMANIS Q9NYP3 Downstream of son gene OFORM 3 protein DPP3_HUMANISO Q9NY33 Dipeptidyl-peptidase III FORM 2 DSCA_HUMANISO O60469 Down syndrome cell adhesion FORM SHORT molecule precursor DTNB_HUMANISO O60941 Dystrobrevin beta FORM 3 EPA3_HUMANMAJOR P29320 Ephrin type-A receptor 3 ISOFORM precursor ERAL_HUMANISO O75616 GTP-binding protein era FORM HERA-B homolog ESR2_HUMANISO Q9UHD3 Estrogen receptor beta FORM 3 F263_HUMANMAJOR Q16875 6-phosphofructo-2- ISOFORM kinase/fructose-2 6- biphosphatase 3 FAFY_HUMANISO O00507 Probable ubiquitin carboxyl- FORM SHORT terminal hydrolase FAF-Y FCAR_HUMANISO P24071 Immunoglobulin alpha Fc FORM B-DELTA- receptor precursor S2 FCE2_HUMANMAJOR P06734 Low affinity immunoglobulin ISOFORM epsilon FC receptor FTCD_HUMANISO O95954 Formimidoyltransferase- FORM E cyclodeaminase FUT8_HUMANISO Q9BYC5 Alpha-(1,6)-fucosyltransferase FORM 2 FXM1_HUMANISO Q08050 Forkhead box protein M1 FORM 2 G72_HUMANMAJOR P59103 Protein G72 ISOFORM G72_HUMANISO P59103 Protein G72 FORM 2 G8_HUMANMAJOR Q9UBA6 G8 protein ISOFORM GBR1_HUMANISO Q9UBS5 Gamma-aminobutyric acid FORM 1E type B receptor subunit 1 precursor GCFC_HUMANISO Q9Y5B6 GC-rich sequence DNA- FORM D binding factor homolog GCP2_HUMANISO Q9BSJ2 Gamma-tubulin complex FORM 2 component 2 GDNR_HUMANISO P56159 GDNF receptor alpha FORM 2 precursor GLI2_HUMANMAJOR P10070 Zinc finger protein GLI2 ISOFORM GLI2_HUMANISO P10070 Zinc finger protein GLI2 FORM BETA GLI2_HUMANISO P10070 Zinc finger protein GLI2 FORM DELTA GLI2_HUMANISO P10070 Zinc finger protein GLI2 FORM GAMMA GLSK_HUMANISO O94925 Glutaminase kidney isoform FORM GAC mitochondrial precursor GPT_HUMANMAJOR Q9H3H5 UDP-N-acetylglucosamine-- ISOFORM dolichyl-phosphate N- GRB2_HUMANMAJOR P29354 Growth factor receptor-bound ISOFORM protein 2 HAIR_HUMANMAJOR O43593 Hairless protein ISOFORM HAIR_HUMANISO O43593 Hairless protein FORM SHORT HFE_HUMANMAJOR Q9HC68 Hereditary ISOFORM hemochromatosis protein precursor I17S_HUMANISO Q9NRM6 Interleukin-17B receptor FORM 2 precursor ICE2_HUMANISO P42575 Caspase-2 precursor FORM ICH-1S ICE8_HUMANISO Q9C0K4 Caspase-8 precursor FORM 7 ICEA_HUMANISO Q92851 Caspase-10 precursor FORM B ICEA_HUMANISO Q92851 Caspase-10 precursor FORM C ILF1_HUMANISO Q01167 Interleukin enhancer- FORM 2 binding factor 1 IRF7_HUMANISO Q92985 Interferon regulatory factor 7 FORM C IRL1_HUMANISO Q01638 Interleukin 1 receptor-like FORM C 1 precursor ITP1_HUMANMAJOR O14713 Integrin beta-1 binding ISOFORM protein 1 ITP1_HUMANISO O14713 Integrin beta-1 binding FORM 2 protein 1 KC11_HUMANIS Q9HCP0 Casein kinase I gamma 1 OFORM 1S isoform KLK2_HUMANIS P20151 Glandular kallikrein 2 OFORM 3 precursor KLKF_HUMANISO Q9H2R5 Kallikrein 15 precursor FORM 2 LEF1_HUMANISO Q9UJU2 Lymphoid enhancer FORM B binding factor 1 LFA3_HUMANISO P19256 Lymphocyte function- FORM SHORT associated antigen 3 precursor LIK1_HUMANISO P53667 LIM domain kinase 1 FORM 3 LSHR_HUMANMAJOR P22888 Lutropin- ISOFORM choriogonadotropic hormone receptor precursor LYST_HUMANMAJOR Q99698 Lysosomal trafficking ISOFORM regulator M2A2_HUMANISO P49641 Alpha-mannosidase IIx FORM SHORT MADI_HUMANISO O95405 Mothers against FORM 2 decapentaplegic homolog interacting protein MAP2_HUMAN P11137 Microtubule-associated MAJOR protein 2 ISOFORM MAP2_HUMANI P11137 Microtubule-associated SOFORM MAP2C protein 2 MAP4_HUMANI P27816 Microtubule-associated SOFORM 2 protein 4 MAX_HUMANISO P25912 Max protein FORM 3 MK11_HUMANISO Q15759 Mitogen-activated protein FORM BETA-2 kinase 11 MLH3_HUMANISO Q9UHC1 DNA mismatch repair FORM 2 protein Mlh3 MRP3_HUMANISO O15438 Canalicular multispecific FORM 3A organic anion transporter 2 MRP3_HUMANISO O15438 Canalicular multispecific FORM 3B organic anion transporter 2 MSRE_HUMANISO P21757 Macrophage scavenger FORM II receptor types I and II MTF2_HUMANMAJOR Q9Y483 Metal-response element- ISOFORM binding transcription factor 2 NK31_HUMANMAJOR Q99801 Homeobox protein Nkx-31 ISOFORM NXF5_HUMANMAJOR Q9H1B4 Nuclear RNA export factor 5 ISOFORM NXFS_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM B NXFS_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM C NXF5_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM D NXFS_HUMANISO Q9H1B4 Nuclear RNA export factor 5 FORM E PHMX_HUMANISO Q96QS1 Phemx protein FORM 4 PHMX_HUMANISO Q96QS1 Phemx protein FORM 5 PML_HUMANISO P29590 Probable transcription FORM PML-3B factor PML PPE1_HUMANISO O14829 Serine/threonine protein FORM 2 phosphatase with EF- hands-1 PPT2_HUMANISO Q9UMR5 Palmitoyl-protein FORM 2 thioesterase 2 precursor PRD7_HUMANMAJOR Q9NQW5 PR-domain zinc finger ISOFORM protein 7 PSA7_HUMANISO O14818 Proteasome subunit alpha FORM 4 type 7 PSD4_HUMANISO P55036 26S proteasome non- FORM RPN10E ATPase regulatory subunit 4 PSN1_HUMANISO P49768 Presenilin 1 FORM I-374 PTPD_HUMANMAJOR P23468 Protein-tyrosine ISOFORM phosphatase delta precursor R51D_HUMANISO O94908 DNA repair protein FORM 2 RAD51 homolog 4 RBMS_HUMAN Q93062 RNA-binding protein with MAJOR multiple splicing ISOFORM RED1_HUMANMAJOR P78563 Double-stranded RNA- ISOFORM specific editase 1 RHD_HUMANMAJOR Q9UQ21 Blood group Rh ISOFORM RHD_HUMANISO Q9UQ21 Blood group Rh FORM 3 RYK_HUMANMAJOR P34925 Tyrosine-protein kinase ISOFORM RYK precursor RYK_HUMANIS P34925 Tyrosine-protein kinase OFORM 2 RYK precursor SCA1_ HUMANISO O15126 Secretory carrier-associated FORM 2 membrane protein 1 SEN7_HUMANMAJOR Q9BQF6 Sentrin-specific protease 7 ISOFORM SFR5_HUMANISO Q13243 Splicing factor FORM SRP40-2 arginine/serine-rich 5 SHX2_HUMANMAJOR O60902 Short stature homeobox ISOFORM protein 2 SNB2 HUMANISO Q13425 Beta-2-syntrophin FORM 2 SNXD_HUMANISO Q9Y5W8 Sorting nexin 13 FORM 2 SON_HUMANISO Q9UPY0 SON protein FORM C SON_HUMANISO Q9UPY0 SON protein FORM E SUR5_HUMANISO Q15528 Surfeit locus protein 5 FORM SURF5A T10B_HUMANMAJOR O14763 Tumor necrosis factor ISOFORM receptor superfamily member 10B precursor T10B HUMANISO O14763 Tumor necrosis factor FORM SHORT receptor superfamily member 10B precursor TM31_HUMANISO Q9BZY9 Tripartite motif protein 31 FORM BETA TNR6_HUMANISO P25445 Tumor necrosis factor FORM 2 receptor superfamily member 6 precursor TNR6_HUMANISO P25445 Tumor necrosis factor FORM 3 receptor superfamily member 6 precursor TNR6_HUMANISO P25445 Tumor necrosis factor FORM 4 receptor superfamily member 6 precursor TNR6_HUMANISO P25445 Tumor necrosis factor FORM 5 receptor superfamily member 6 precursor TPA_HUMANISO P00750 Tissue-type plasminogen FORM SHORT activator precursor TPO HUMANMAJOR P40225 Thrombopoietin precursor ISOFORM TR12_HUMANISO Q99831 Tumor necrosis factor FORM 12 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 3 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 4 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 5 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 6 receptor superfamily member 12 precursor TR12_HUMANISO Q99831 Tumor necrosis factor FORM 7 receptor superfamily member 12 precursor U7I3_HUMANISO Q9BYM8 Ubiquitin conjugating FORM 2 enzyme 7 interacting protein 3 U713_HUMANISO Q9BYM8 Ubiquitin conjugating FORM 4 enzyme 7 interacting protein 3 USH3_HUMANISO P58418 Usher syndrome type 3 FORM B protein WS14_HUMANISO Q9NP71 Williams-Beuren syndrome FORM 5 chromosome region 14 protein XE7_HUMANISO Q02040 B-lymphocyte antigen FORM SHORT precursor Z236_HUMANISO Q9UL36 Zinc finger protein 236 FORM A ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 1 ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 2 ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 4 ZAN_HUMANISO Q9BXN9 Zonadhesin precursor FORM 5. 8. The product of claim 7 wherein the dataset of target putative protein isoform sequences comprises isoforms of Calpain-10, CLK1, CLK2, CLK3, and LARD/TNFRSF12.

Details for Patent 8,014,953

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2039-02-26
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2039-02-26
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2039-02-26