NON-INVASIVE DETERMINATION OF METHYLOME OF FETUS OR TUMOR FROM PLASMA

摘要

#$%^&*AU2020200128A120200130.pdf#####ABSTRACT Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cellfree DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer. 12010060_1 (GHMatters) P94865.AU.21/68 P- 0o (N cc ucu (1 , 1 cz to N N c t en (00 10( 2~~~c'c 1.0cc - c 0 cc (0 c n(c 0- 0, 'm( W - c ~ (~ m1 (1- a, (N - occrN ~~~~ OO 0(( WW c ( W ~~~M OD-t ~ crc (0 c4wcA 2c 0 C), r(0( C(0 t-0C - cc (W 00 (A cc4 '0n(0(0(0 cN ~W0(~ CM(0 (0 LN 'D L' LU cc 0 r41 ,( (-4 a) (1 ( Q . +(40' ?2D uj uj (cIfOmm IN~ IX No -nC o r Da cc cc c4 2o cc~C - (12 - ( 1Dc ( (Z: co 'o WP mm r~ mc cc ~,.0Cto , a; c t- - (6 -c cc occc 0 r- (0N I - NIn C(N (1 to, _ A W0( W- (N 10- cc CD -Nr4 C mN (N w0 (1'. N10CN coc c0i w0 (100 I, P,- C co 0. 0 In U4 (314 cl co ( 00 'tC 0) Lo w CNo 0 OD0 0 , 'D CQ, o 02 a, 0)4 j '2 22oU (3 00000 3 3 3C UU o3t 3 3 1 00.... 0 0 (N .l)D ~ ) Z ~ Z U U U U2/68 C')) (0 a)N Tn 0 r- (C) CO (0 C,) c ' 0 IT) CD) U) ~U) 0')(0 C 00 CO (Y (1)~' U ~ ~ ~ ' C ~ ~ ~ ~ c M*0 )N.- o T .CD "; (0 0 -r C') CO4 (T) 060 - 6 c 0o 00~ COU 0f 0 0 :00)g(D N vr co D'Cc'4 co C Coi r- D O co C)) C-) toC V0 q; (1 I . to M~g tr E; N. M o N.-'j S )( T - C'o (0 C(iC') 6 U)(0 & (ID CO co(1 t ( (, NUID)DC LO 0) LO a) C C, coQ to) CO U a CO N. m to W 0 _ 0 0o -0 a nC) f- D C 2I 00 . COC 04 ai -MU) T"006a o) co~ 0 Uo co4 O'4 m- l C-4 (D ') co) a) 0 U') to) o(' CN mV -x U) () C'IT) C a)C')l 0("N oUmom e) co O (0 00 D)l oc n ' '4. 00 0 'S 0 aO~ ) ) o M 6' ai 0 , -:U) C ~ a -C, C-4 m6 (f (D 6C; (0 6- o (ic I- m0 m' too 'n to v *0 U ~ N (::) U) 0O~ C4. (0C) -) C~ "O Ul a)-ja o c )A - 0 N; o 1 0 TrU o (0 Ul a)(_ oC CO r-t fl C C C0 4 -0 00 oU'. oo 0 W0r O(D (D E c~ ~ 222 2 U2)0 cc) m. 0o to (1 U) a) aio ~ o o 00000 t3/68 01 Olt~ d 4U