US 20200187851A1TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No .: US 2020/0187851 A1 Offenbacher et al. (43 ) Pub . Date : Jun . 18 , 2020 ( 54 ) PERIODONTAL DISEASE STRATIFICATION (52 ) U.S. CI. AND USES THEREOF CPC A61B 5/4552 (2013.01 ) ; G16H 20/10 ( 71) Applicant: The University of North Carolina at ( 2018.01) ; A61B 5/7275 ( 2013.01) ; A61B Chapel Hill , Chapel Hill , NC (US ) 5/7264 ( 2013.01 ) ( 72 ) Inventors: Steven Offenbacher, Chapel Hill , NC (US ) ; Thiago Morelli , Durham , NC ( 57 ) ABSTRACT (US ) ; Kevin Lee Moss, Graham , NC ( US ) ; James Douglas Beck , Chapel Described herein are methods of classifying periodontal Hill , NC (US ) patients and individual teeth . For example , disclosed is a method of diagnosing periodontal disease and / or risk of ( 21) Appl. No .: 16 /713,874 tooth loss in a subject that involves classifying teeth into one of 7 classes of periodontal disease. The method can include ( 22 ) Filed : Dec. 13 , 2019 the step of performing a dental examination on a patient and Related U.S. Application Data determining a periodontal profile class ( PPC ) . The method can further include the step of determining for each tooth a ( 60 ) Provisional application No.62 / 780,675 , filed on Dec. Tooth Profile Class ( TPC ) . The PPC and TPC can be used 17 , 2018 together to generate a composite risk score for an individual, which is referred to herein as the Index of Periodontal Risk Publication Classification ( IPR ) . In some embodiments , each stage of the disclosed (51 ) Int. Cl. PPC system is characterized by unique single nucleotide A61B 5/00 ( 2006.01 ) polymorphisms (SNPs ) associated with unique pathways , G16H 20/10 ( 2006.01 ) identifying unique druggable targets for each stage . Patent Application Publication Jun . 18 , 2020 Sheet 1 of 56 US 2020/0187851 A1 20.2 11.2 27.4 12.1 23.0 31.4 10.8 18.7 24.6 24.9 26.0 27.3 44.9 byPPCandTPCofThreeorMoreTeeth10-YearToothLossProbability 1.FIG 11.1 21.9 253 30.7 8.7 11.5 22.7 72 5.4 TPC-A -DTPC TPC-F Patent Application Publication Jun . 18 , 2020 Sheet 2 of 56 US 2020/0187851 A1 IPR FIG.2A OZ K ?!!! qeqoid Patent Application Publication Jun . 18 , 2020 Sheet 3 of 56 US 2020/0187851 A1 ROC:0.72 Specificity 2BFIG. Araqsuas Patent Application Publication Jun . 18 , 2020 Sheet 4 of 56 US 2020/0187851 A1 IPR FIG.2C 20 K !!!! qeqoid Patent Application Publication Jun . 18 , 2020 Sheet 5 of 56 US 2020/0187851 A1 teorie ROC:0.72 Specificity FIG.2D Kiran suas Patent Application Publication Jun . 18 , 2020 Sheet 6 of 56 US 2020/0187851 A1 IPR FIG.2E Al! l ! qeqoid Patent Application Publication Jun . 18 , 2020 Sheet 7 of 56 US 2020/0187851 A1 1,00 ROC:0.75 Specificity 2FFIG. *** Al! a !!!suas Patent Application Publication Jun . 18, 2020 Sheet 8 of 56 US 2020/0187851 A1 IPR FIG.2G ?? ???eqoad Patent Application Publication Jun . 18 , 2020 Sheet 9 of 56 US 2020/0187851 A1 00 ROC:0.68 Specificity FIG.2H A1! A !!!suas Patent Application Publication Jun . 18 , 2020 Sheet 10 of 56 US 2020/0187851 A1 + www + accom G m G XS E 208838 D D A suten 192212213/2019:1915/1816/1711322313130_4293286227/268/259/2220/23 D einen A F 1322313304/2932861271268/2592410/2311/2212112014:1915/1816/17 24916.024.918.710.810814514.5 24918.7145|14.510.824.9 FIG.3 D enam tentang he ca D ??? E G E E w Patent Application Publication Jun . 18 , 2020 Sheet 11 of 56 US 2020/018785 ] A1 8??? E-???? S60????????? 850???? 1980S60S80Tz50s60888888888888888888888888888888888 (7/91)SC/STGODT02CTTOWEU01DUGGYUYADUBUS630001012000 88080601058020:4380088 60 L60 ????????????? 60 60 8888888888888888888&8888609038888888888888 60 8 60 FIG.4A 60 88 600 880 550 [st2sotsolato1950sols60 8030EEG36060 888888888888888888888888888888888 8888888888 88000888888888888888888888888888888 ?????????0??? 888 & Patent Application Publication Jun . 18 , 2020 Sheet 12 of 56 US 2020/0187851 A1 000 2000 02 DO |10 0.07008 12 0.120809 DANS0.19 0.120.07 DO 00:00 00000 SOBO PORNO GIO 0.05 (1/9T8USTGTMOUTTOTCUTIEUOTTUGSURO,LugBUSCON00€WEIT 002502002210.000.12DORT 2000800709001200ILOILOSOPS0012001200200 000 38800300030.140.10.0810031OUOO0.11 FIG.4B DOKTOTO320158013SVO9001810STOTU0U201580000000 000 000080.120.140.110080.15 0.01005100900210020020.030.180.130050030020002002 0030330220000220002001 03830.03 GOOOOOOOOOOO6000 3 wa 3 Patent Application Publication Jun . 18 , 2020 Sheet 13 of 56 US 2020 / 0187851A1 088 88 88 0 87 88 88 ?????? 0&???????????? 50008808888888888888888888888888880450 200808080000010830382050-88806603213 302928888888888888888888888888888888888888 8008080-50-3036502480 8 88 0 88 1002008700006701501600SPOLEHL77027012001500000 80%8888015802802812822838 1930[ES00 0 0 0 8888888888888888888888888888888E° 0 88888888888888888888888888888888888888840 888888888888888888888888888888888888888888 0 0 08288888888888&ttpst}?8* 70800900T FIG.4C 0 0 0 ?????&0 1388880: 30 ?????88888888888888888888888888888888888888888 ? -"? 888 % . Patent Application Publication Jun . 18 , 2020 Sheet 14 of 56 US 2020/0187851 A1 6001901190001900 0.16003004 0122002011on01307. 0.540.25049057035)051]0310.36 0,090070091006005000080061003004 0231051097049091003802810900300:301240104410431090901020 CassMoniker1/22010/2014295/2816/222/2016/289/24102)11/2212211920191919/18/16/17 009020330.15003002)0010010010001902.002011_023_0320 0.050.070.000.000070.04004100510.1010.0810.001 0.16000330340.60.1410010.081011B0281094090.16 0.000.010.160.1101101100101410.20000091002 0.2510930920530500410350.250.2610310351051105710491099026 000000000 00310010001001000 00080290920220.200.110.120.10 FIG.4D 0080]008009 041040.550.500.570.25 ScoresHighl 00000000000000000000OOOOOOOOO Cornie Whe Patent Application Publication Jun . 18 , 2020 Sheet 15 of 56 US 2020/0187851 A1 60?? 170 150To$0 80 80 80 600.000.000.00 1270 80 28&880850803888888888888888888888888 to80000600OTSOELOETOTO??11?11??1?????0 003010100201033109310510420.210.20.3302010000.091 e]80 2880188888888888888888888888888888888888888888888888888888 EXON76SUS9/110/9RUS62/06&taxouONOMOD(1OTSTGTTerturitur1 EXO990690198919901909190190.65USD10 ?????1000020010 8032016016606001990/60/200STOB0 4E.FIG 000200100COD30000 OOOOOOOOOOOOOOOOO00000000000000000 (180|130V7019901501950198010MUUD21013801180PO1990199 ??;088-804808348508 STO weit Writer Patent Application Publication Jun . 18 , 2020 Sheet 16 of 56 US 2020/0187851 A1 2008 00DO500POSTO1620 00103002)0030 000030000150.000 37037060060103603203290103603803009 9701997OSOB20301980158006090120 1990000990650 100600koolmolorolate1200600/60sottoloeo800 OVO880000109009060SUOVODIGIOPID ö165019501901990290300ECO6501090 ClassMoniker132013/2014295/286/27/7/208/259/24/10/2311/2212/2113:2014/1915/1816/17 8820230????&???????2008 100UNDCOO90090OLONOIONOTOOPOORODLO200 0670800900900001900T0 FIG.4F 08303842083 DO200LEDLOEEDEDCORCO 607501307801937 000160.0002000000300 : ????????? Toothloss 3 Patent Application Publication Jun . 18 , 2020 Sheet 17 of 56 US 2020/0187851 A1 20 1250150310 6600630 00012 003)00021026038033 0.1002302202902201301000900022032043051) DO0TO 000 9001998199919901991UL1899190120 LI/ATBTSTGIMT02CTTZZTEZTEZOTTUGSZ8B22ELAEZS1622088.TERZENTTRIUOMISep LETOISTOBIOITO 200910910SIO000MOQUOSTO20.STODUODIOSTO200 50018009001200ITOSIO100W0QUOETO 000000000.00.000.000.000.0001000 FIG.4G 031032022017 0.150.000 ***** has 0 Patent Application Publication Jun . 18 , 2020 Sheet 18 of 56 US 2020/0187851 A1 DARIC:DistributionofToothProfileClass(TPC) Class(PPC)PersonProfileby FIG.5 Patent Application Publication Jun . 18 , 2020 Sheet 19 of 56 US 2020/0187851 A1 0091839 010002101925 462_353_2004_42448977385082981783273047.143423.439.9523 6284222748.1202202_3572878.310.81201221159430338 636427.110000405091318258.15.162 43927020.3_46.1.65.9_80083076077.2835_842_604_474_18825.1:402 31891561481223246401451547919410653 10,010,71288.336919212311.817.48.2124169159102 00_00_01_01 103_20.02.14.u081911227.0400_32814,8132282339252 16.920016642640109030149008422220.7InterproxDis256 6021524026.828.528127093305.02022 TPC1/3221313/304/295/286/277/268/259/2410/2311/22122113/2014/1915/1816/17Descriptor 6AFIG. 88019023000000252558033 4510 05 GSevere Patent Application Publication Jun . 18 , 2020 Sheet 20 of 56 US 2020/0187851 A1 060707003097.71962481705:4 163.13,98.25.54.1522210040512 10040102030.101.13276.510.0216042 17713011335552884280354950264268.958.535011.119.2 9214,8759.715.416.212.39.816.07.5 9616.523.718.15010.010.8.11.81160.120,4242190_123_52 8178841079.718.425.919,314,0105991038.27259 20315.88615.015.624.523.822.019.018.517.512012898192 48.140140.813.65.9.12.18.03.02.08.04.3.714.1411424433 867.764.09.09.03.01.0102030101006588 1/322/313/304/295/286/277/268/259/2410/2311/2212/2118/2014/1915/1816/17TPCDescriptor 305.610.17413.51182432394114,813,87110,9733.1BRecession 28.529.511.220.2207.8131209087.52231215.6InterproxDis38.1367E 279196152388_48.0_6887799758_757078483_424_198214233 FIG.6B 411812421757600007 ToothforPPCMildDistributionofTPCby Patent Application Publication Jun . 18 , 2020 Sheet 21 of 56 US 2020/0187851 A1 4.53.7 502 5.38.511.84.13.7 44961431072708.080515 S75.111.311015.2185.35.63.723 7478173182.72.94.1249,95.96.829.4.12231 12.710.15.12540337.1534.6207.97.813.59.5191.9 1128141050303113.10016262.9039 00368.9110150751113.915.11187011513.39.98.025 11.95.938230923,816.51456.38.714,717.219.115204.1 6.998581034207223238248234195196100111 492519271828509528524492_490_517_29.948.551.8436422_570 444237627.413.518.2InterproxDis5.5777612.2E17.415.2 5.56.07.88.87.05.38.511.820437.21218.1 FIG.6C 3933325675603 55760251.547.543549058.3617603580574_524_452_475_509 68294127243118 22516612.390424633