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C19) United States C12) Patent Application Publication C10) Pub 1111111111111111 IIIIII IIIII 1111111111 11111 11111 111111111111111 1111111111 1111111111 11111111 US 20200081016Al c19) United States c12) Patent Application Publication c10) Pub. No.: US 2020/0081016 Al Talaat et al. (43) Pub. Date: Mar. 12, 2020 (54) BIOMARKERS FOR EARLY DIAGNOSIS Publication Classification AND DIFFERENTIATION OF (51) Int. Cl. MYCOBACTERIAL INFECTION GOIN 33/68 (2006.01) C12Q 116851 (2006.01) (71) Applicant: Wisconsin Alumni Research GOIN 33/569 (2006.01) Foundation, Madison, WI (US) (52) U.S. Cl. (72) Inventors: Adel Mohamed Talaat, Madison, WI CPC ......... GOIN 33/6854 (2013.01); GOIN 33/68 (US); Chia-wei Wu, Madison, WI (US) (2013.01); GOIN 2800/50 (2013.01); GOIN 33/5695 (2013.01); GOIN 2800/26 (2013.01); (21) Appl. No.: 16/555,819 C12Q 116851 (2013.01) (22) Filed: Aug. 29, 2019 (57) ABSTRACT Mycobacterial-specific biomarkers and methods of using Related U.S. Application Data such biomarkers for diagnosis of mycobacterial infection in (60) Provisional application No. 62/728,387, filed on Sep. a mammal are disclosed. 7, 2018. Specification includes a Sequence Listing. Patent Application Publication Mar. 12, 2020 Sheet 1 of 10 US 2020/0081016 Al FIG. 1 ·~{:: -{t i * !lpNbiNi$ 1 !lpN p~ra 111:111111 llillllll: 111!11,111llltllllll~ 11111 ■111 ~; C,,Nmnsus KR.IGINMTKX L.lC(X.AXXXXG AXXXXMPXTX RXO-GXVXXVG VKVXPWIPTX ® • ® l I I iipN lK>V(S ~Hl!lli!Wiofflij 1!11.llofJiillj mllB~lijftlt flol=fiolill ••t-il-~MM ~9 llpN p~ra HfHJoffit:torti ilffllGNillm miJllt~ttiollf ~•01:101111 llm:l:l1IA@~ iOO C,,nstmsus XXRXLXXGRS Vt IOGNT.LDP i LOt.MLSXXR XXGXOG.I...XVO ODXXXSR:AXM t2:;: i-/4~~ ! l 1 I~~~~b;:: llllil~l:1:1 llil 111111:1~:111~ 1111111::;1 1lllilllll: ~:~ C,,nimnsus XXXXXXXPGP QtHVDVXXI...X XPGPAGXIPA RHYRPXGGXX QXPt.l...VFYHG Consl:lrvat,ofl -:§;::. .{;;-:;: 2-/4{~ ! -: lipN Mvlii ■,Htl\ilftffl 80~1;01ffl\il Gtlij!~Got!lt mHMBll~III @111:aommmi 248 !ipN pam ltWAHfb.rn;o ·I ffioA!.lffioffitAll ooiffAGGfdMi #WlttiAII# · · -, ·GGffiASI 245 C<m$0rn,us XWAHEHA.XOE .XGAXPGRVAV GGOSAGGNLX AVVKQLAROX AR:YEGGPXPV :1::K> ~~=~<~ ! j !lpN b<1Vi$ llllilRllil.ffiB ijofj~ffiiRl.li:I AoBft!tlffilBo iililiillti omAl:18111:s 348 UpN pm;;i IIIW:iillill AalAiilRII AGl!l!iiiilG ffi!iiii~DIAA ot:m1:111111~ 345 CMBl:lf';Bus R:XSPXLAE$L XGLAPAt I AV AGFDPI...RDEG XSYAXALRAA GTXVOtRYLG :E:, :m::, ~ ~ 1ipN b<1vis illibislIIHII ffilGoGiKAGI ililli*RIIH iill 3~ tipN pm;;i i!lfi.GiAi!II i!IGGlii~jij!f il.lffl!jijfflffii{ij iiil'iJi 3W CMBMS!JS SI... THGFXNLF QI...GGXSXXXT· XE.l I SAL RAH I...SRV Patent Application Publication Mar. 12, 2020 Sheet 2 of 10 US 2020/0081016 Al FIGS. 2A-2B A. 1 Q Ii N B. 3 Patent Application Publication Mar. 12, 2020 Sheet 3 of 10 US 2020/0081016 Al ... <l) ,;,: Ct1 c:; (I) > Y'J 2 (lJ i::: 'O (.) tlj .::- ...(I) Q,, 0 0 >- ~ d. ·o"' @ ·o 0 ~ E 0 § ,c:. .. u 0 C <ti Q) 2 C) S? 6 ..,-, 0 9. ·- FIGS. 4A-4C ""O ~..... ('D =..... A B t"e Infected vs. LAV­ .... LAV-vaccinated vs. (')- Infected vs, na!'ve na'ive Infected vs. naYve vaccinated ~......... 0= =""O O".... (')- ~......... 0= ~ ~ :-:.... N ~ Total analyzed genes: 17,380 Total analyzed genes: 17,380 N 0 N 0 rJ'1 ('D=­ LAV~vaccinated vs, Mycopar-vaccinated ('D..... naive vs. nalve .i;... 0 C .... 0 c rJ'1 N 0 N 0 0 0--- QO.... 0.... 0-1 Total analyzed genes: 17,380 >.... 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MYCOBACTERIAL INFECTION SUMMARY OF THE INVENTION CROSS-REFERENCE TO RELATED [0009] The present invention overcomes the aforemen­ APPLICATIONS tioned drawbacks by providing a set of biomarkers to [0001] This application claims priority to U.S. Provisional diagnose infected animals and distinguishing between vac­ Patent Application No. 62/728,387 filed Sep. 7, 2018, which cinated and infected animals. is incorporated herein in its entirety. [0010] In a first aspect, provided herein is a method for diagnosis of mycobacterial infection in a mammal, the STATEMENT REGARDING FEDERALLY method comprising the steps of a) obtaining a first type of SPONSORED RESEARCH sample from the mammal; b) measuring the expression level in the sample of at least one biomarker selected from the [0002] This invention was made with govermnent support group consisting of LOC108634521, LOC108637251, under 2013-67015-21347, 2018-67015-28243 and 2016- LOC108637252, LOC108634594, FAM198B, 33610-25438 awarded by the USDA/NIFA. The government LOC108637671, CDCPl, TMTCl, BAIAP2Ll, MEIi, has certain rights in the invention. SEPTl0, IFNG, IL17F, FCER2, ADGRGl, APBBl, PIWIL2, AOAH, and homologs thereof and comparing the REFERENCE TO A SEQUENCE LISTING level
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