US 11,946,928 B2
Methods and compositions relating to airway dysfunction
Ke Xu, Cambridge, MA (US); Marc E. Lenburg, Brookline, MA (US); Ehab Billatos, Milton, MA (US); and Alejandro A. Diaz, Boston, MA (US)
Assigned to TRUSTEES OF BOSTON UNIVERSITY; and THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
Filed by TRUSTEES OF BOSTON UNIVERSITY, Boston, MA (US); and THE BRIGHAM AND WOMEN'S HOSPITAL, INC., Boston, MA (US)
Filed on May 19, 2022, as Appl. No. 17/748,404.
Claims priority of provisional application 63/191,080, filed on May 20, 2021.
Prior Publication US 2022/0373537 A1, Nov. 24, 2022
Int. Cl. G01N 33/50 (2006.01); C12Q 1/6883 (2018.01)
CPC G01N 33/5023 (2013.01) [C12Q 1/6883 (2013.01); C12Q 2539/10 (2013.01); C12Q 2600/118 (2013.01); C12Q 2600/158 (2013.01); G01N 2800/50 (2013.01)] 28 Claims
OG exemplary drawing
 
1. A method comprising detecting the level of expression of one or more genes selected from at least one of:
at least one gene of Group A, at least one gene of Group B, at least one gene of Group C,
at least one gene of Group D, and at least one gene of Group E;
in a bronchial brushing, nasal brushing, or sputum sample obtained from a subject; and
the level of expression products of no more than 100 other genes is determined;
wherein:
i) the at least one gene of Group A comprises Zinc Finger Protein 493 (ZNF493);
ii) the at least one gene of Group B comprises Fat Atypical Cadherin 2 (FAT2);
iii) the at least one gene of Group C comprises at least one of: Argininosuccinate Lyase (ASL) and Coiled-Coil Domain Containing 160 (CCDC160);
iv) the at least one gene of Group D comprises at least one of: Long Intergenic Non-Protein Coding RNA 888 (LINC00888) and F-Box Protein 16 (FBX016); or
v) the at least one gene of Group E comprises DnaJ Heat Shock Protein Family Member C22 (DNAJC22); and
wherein Group A consists of:
ZNF493; ZNF519; ENSG00000271430; MYH7B; MKRNSP; ENSG00000270574;
VN1R83P; ENSG00000268555; ZNF577; NBPF11; SCUBE2; SGK2; BNIPL;
ENSG00000271533; PCDHGB6; LRP1; PCDHGB7; ENSG00000262877; ABCC5;
PMS2P4; TTC28-AS1; PRR24; CD81; RGL3; PTPRS; ENSG00000271011; ZNF286B;
GNB1L; PCDHGA12; SLC16A10; ZNF66; ENSG00000261584; ZNF311; ZNF718;
ENSG00000223745; RAB40A; ENSG00000268119; PCDHGA4; ENSG00000270589;
ENSG00000256142; DLL1; BRAFP1; PCDHGA11; FTX; FLYWCH1; NOVA1;
KANSL1; ZNF826P; ENSG00000196295; ENSG00000229036; TLE3; KLF8; LONRF2;
PCDHGB8P; ENSG00000259326; AOC2; RAPGEFL1; ARL10; ADAMTS10;
ENSG00000250303; TSHZ2; CRYM-AS1; ENSG00000213971; TVP23CP2;
ENSG00000234978; ZBTB12; PCDHGA9; RPS3AP29; KSR2; ENOSF1;
ENSG00000233175; ENSG00000260729; LINC00664; ZNF257; POU5F1P5; FN3K;
ZNF814; CYP2C19; ENSG00000270096; PDE11A; FAM13A-AS1; KCNMA1;
ENSG00000247270; ENSG00000270019; ENSG00000270154; ENSG00000248445;
ENSG00000234129; ENSG00000267169; ENSG00000261423; C1RL-AS1; NONOP2;
SLC26A5; STX18-AS1; AMT; ENSG00000232626; ENSG00000235834; RN7SL648P;
ENSG00000254634; ENSG00000236144; ACAP2-IT1; ENSG00000268472; TDRD6;
ENSG00000272563; SUDS3P1; PCDHGB4; FOXO3B; ENSG00000272977;
LINC00176; MY015A; GHRLOS; TTC28; ENSG00000271840; NBPF20; VANGL2;
JMJD7-PLA2G4B; ENSG00000267940; OGDHL; ENSG00000206195; KLF11;
TAPT1-AS1; TMEM59L; ACKR3; ENSG00000184441; KAT2A; SULT1A3; SIPA1L2;
RPL5P4; CTSF; ZNF208; CYP2E1; L3MBTL1; BENDS; ACACB; ENSG00000261087;
NFATC4; CES4A; ZFP2; BSN; ENSG00000254469; ZNF514; ENSG00000176593;
ENSG00000232116; OTX1; ENSG00000269918; AVIL; ENSG00000271971; MICU3;
GRAMD1A; C1QTNF6; KIF3C; ZACN; RPL7P46; PLA2G4F; SLX1A-SULT1A3;
ZNF135; OR2A9P; TMEM63C; TG; ENSG00000261502; ARLSB-AS1; ZNF705E;
PCDHGC5; GOLGA8A; PLEKHH1; PPAP2B; ENSG00000267481; OR7E7P;
ENSG00000259585; ENSG00000225210; TSSK1B; ENSG00000215022; STRC;
ENSG00000250290; UBAP1L; ENSG00000264112; LINC00959; SPATA41; CRYGS;
ZNF862; ENSG00000225032; PCED1B; SMAD6; ENSG00000264538; FRS3;
ENSG00000256139; NSUN5P1; LTBP4; ENSG00000267053; ENSG00000171282;
PCDHGA7; GREB1; ADAM1A; ENSG00000251323; ENSG00000271917;
ENSG00000253366; ENSG00000225241; IL11RA; PCDHB18; FAM85A; UPK3BP1;
ACADL; ENSG00000236055; ZNF285; and ENSG00000239665;
wherein Group B consists of:
LRP4; ZNF578; FAT2; FGFR3; MCC; SLC26A9; MKL2; AGKP1; KRT15; CSRNP3;
PKP1; FSTL3; NEURL1; JAG2; DACT2; TRO; NDRG1; ADCY2; IGSF3; NLGN4Y;
SALL2; SUSD4; ARSG; BCL11A; RNF165; TP63; UGT1A7; CACNA1A; PAPPA;
SULF2; RGS17; PIK3R1; SNX31; COL4A5; SNAI2; UGT1A5; SYNGR1;
ENSG00000213963; SV2A; FGFR2; KANK1; WNTSA; FZD7; SRRM3; SEMASA;
ZNF471; HYKK; PPM1L; ARHGAP28; UGT1A8; ARHGEF10; MT1X; FOXN1;
NTF3; SMOC2; USP44; FBXL16; EPAS1; EGFR; PTPRG; NEB; GDNF-AS1;
FAM117B; RERG; ZBTB47; ADAMTS9-AS2; PAPLN; NCKAP5; STK32A; FAT4;
LGR6; TPTE2P1; SLITRK6; TNC; EVPLL; POMGNT1; KCTD15; WSCD1; KIF7;
KIF1A; FRAS1; KRT5; ENSG00000174171; CDH11; ZFP28; GPRASP1; PRKY;
COL4A6; LSAMP; SYDE1; ENSG00000271880; RGMA; BOC; SLC2A9; WNT2B;
CDHR1; ENSG00000248705; TGFB2; NCAM1; LTB4R; TLE2; AP3B2; LRRC2;
MEGF6; RNF212; FBLN1; SLCO4C1; WNT3A; ZNF665; ESYT3; FREM2;
ARHGEF4; LURAP1; SETP21; COL7A1; B4GALNT4; FBN1; ZNF90; LRP1B;
ABCC9; ENSG00000256995; S1PR5; EFS; NPTX1; ENSG00000260197; UGT1A2P;
SLC16A2; MAN1C1; MARVELD1; FGF9; CIB2; LGR5; KIRREL; LTB4R2; SPTB;
ITPRIPL1; PHLDB1; SPRY1; DEPTOR; EPHA4; TTTY10; TET1; ZNF667; EPHB6;
ENSG00000250685; ENSG00000271738; IGFBP4; ARHGEF25; TRPV6; KCNB2;
SPRY2; DLK2; and CLUL1;
wherein Group C consists of:
ENSG00000258545; ENSG00000257512; ASL; CCDCl60; SMIM6; PLCB1;
TMEM125; C20orf201; CD38; ENSG00000268129; TSPAN2; DAPP1; IDH2; APOL4;
HRASLS2; C9orf66; BFSP1; DLG1-AS1; C16orf54; LAMP3; LYSMD2; PSMB9;
NR5A2; ENSG00000005189; COCH; CCDC67; XK; OR7E14P; LINC00589; F5;
PDE3A; RTP4; ENSG00000253474; ANTXR2; HCG4P3; FATE1; FBLN5;
ENSG00000259153; NMI; ENSG00000231901; PSMB8; SERF1A; MOCOS; GSTM1;
RAMP1; LINC00643; PRKG1; ENSG00000225335; LMO3; ENSG00000270659;
CNTF; ENSG00000272463; ENSG00000260552; FHL1; KIF18A; RARRES3;
TNFAIP8L3; PSMB10; ENSG00000227053; DPF1; GSTT2; TMEM176B; RPL7AP64;
CDKN2D; ENSG00000196826; MUC12; ENSG00000260806; GLIPR2; USP18;
ENSG00000238837; Cl9orf38; ABCC2; VWASA; SGOL2; PKIB; KLB; TMEM200C;
and SHH;
wherein Group D consists of:
LINC00888; FBX016; SCRN1; ENSG00000259508; LINC00467; MPC2; KIAA0895;
SEPW1; CALML4; ERICH2; SLC51B; FAM69A; ENSG00000259802;
ENSG00000249241; MRPS31; CCDCl76; DUSP14; TMEM17; VIM-AS1; GSTP1;
CCT6B; RUVBL1; ENSG00000267325; AAED1; SLC25A4; Clorf192; DYRK3;
ELK3; ENSG00000272092; LINC00326; B9D2; LINC00240; IFT43; CPNE8; SMIM22;
PHTF1; Cllorf70; APOO; SPAG1; CCDC65; DPCD; CCDCl04; RABL5;
ENSG00000263450; DNPH1; ENSG00000234478; ENSG00000233170; LINC01132;
IQCK; ENSG00000257698; ROPN1L; AHSA1; C21orf59; C15orf65;
ENSG00000271133; IL7; LXN; DNAL4; C6orf99; MAPS; Clorf189; LINC00948;
DHX40; GFM2; LRRC34; SPA17; ENSG00000261465; C21orf119; TUBA1A; GJB7;
TOMM34; NUDT7; LINC00908; ClOorf107; C20orf85; ARL3; DNAL1; CNTN5;
MYCBP; ENSG00000266916; ENSG00000260057; CYSTM1; ENSG00000236028;
UFC1; C9orf135; ENSG00000263011; DSTN; IFT57; C9orf116; MORN2; PPIL6;
LCA5L; DPY30; CEP97; AKAP14; ENSG00000272514; CAPSL; CC2D2A; OSCP1;
DYX1C1; PNLDC1; SPATA4; ZNF165; IGFBP7; CXorf58; C15orf26;
ENSG00000224049; TCTEX1D2; TCEAL3; ENSG00000258940; DYNC2LI1; and
PKIG; and
wherein Group E consists of:
C8orf76; DNAJC22; ENSG00000250508; SEC23B; SLC35B1; KRT23; MRPL47; NIP7;
NDUFV2; KCTD14; GTF3C6; ISOC2; SAP30; HSBP1; PSMA5; ENSG00000262823;
SEC61B; TIMM17A; CLIC5; RPN1; LACC1; MRPL54; PSMB5; UCHL3; C14orf166;
C2orf47; PPP1R2; C5orf15; DNAJA1; HIGD1A; MIF; RAB9A; CASP7; POMP;
SERHL2; BCCIP; GRK5; UBB; PARK7; CHCHD2; FAR2; DNAJC12; NT5C3A;
UFM1; CDK7; CCDCl67; CCT2; MORF4L2; CALM2; C4orf19; PSENEN; HSPA8;
GTF2B; NDUFAB1; DAD1; SMS; KBTBD4; AGR3; GPR160; TCP1; PSMA3; STS;
LAMTOR5; COX17; UGCG; PSMA6; COX6A1; SLC41A2; HSP90B1; PDIA4; NXT2;
LACTB2; RFK; DYNLT1; COX7A2; BOLA3; MTFP1; FOLH1; PSMD10; NDUFB4;
MRPL39; Clorf122; MMADHC; SEC61G; NDUFB3; SSR4; NRIP1; ANG; WBP5;
ABRACL; BIK; MRPS36; MOSPD1; SLIRP; MRPL13; CD24P4; ENSG00000113811;
LINC00493; SOD1; IGFBP6; PRDX4; ACTR6; SDF2L1; C19orf10; IL23A; BZW1P2;
CXCL17; and USMG5.