鐢熶俊鎶€鏈?/span>

杩欓噷闈㈡秹鍙婂埌鐨勪竴浜涘悕璇嶇殑鍚箟锛屽洜涓烘病鏈変竴涓‘鍒囩殑涓枃鍚箟锛屾墍浠ュ湪鍚庨潰鎴戜細鐢ㄥ叾涓竴绉嶄腑鏂囧惈涔夋潵琛ㄧず锛?em>Consensus Sequences : 鍏辨湁鎬у簭鍒楋紱涓€鑷存€у簭鍒楋紱涓€鑷村簭鍒?em>Sequence Motifs : 搴忓垪鍩哄簭Consensus Sequences : 涓€鑷存€у簭鍒?em>The Motif Finding Problem : 鍩哄簭鎼滃闂

搴忓垪鍩哄簭鍙婂叾鐢熺墿瀛︽剰涔?/h1>

搴忓垪鍩哄簭(Sequence Motifs) 鏄垎甯冨湪鍩哄洜缁勪腑鎴栧熀鍥犵粍鍐呯殑鏍搁吀搴忓垪锛屽叿鏈夋垨鎺ㄦ祴鍏锋湁鏌愪簺璋冭妭鎴栫粨鏋勭敓鐗╁鍔熻兘銆?/p>

鍦ㄥ熀鍥犵粍鐨勪笉鍚岄儴鍒嗭紙濡傚鏄惧瓙銆佸唴鍚瓙鍜孌NA涓笉缂栫爜铔嬬櫧璐ㄥ簭鍒楃殑鐗囨锛変腑鍙戠幇鐨勫熀搴忓叿鏈変笉鍚岀殑鍔熻兘銆?/p>

澶栨樉瀛?鍩哄洜缁勭殑缂栫爜閮ㄥ垎) 涓瓨鍦ㄧ殑鍩哄簭鍐冲畾浜嗚泲鐧借川鎴栨爣璁拌泲鐧界殑缁撴瀯锛岃繖浜涜泲鐧借川鎴栨爣璁拌泲鐧藉皢琚彂閫佸埌缁嗚優鐨勬煇浜涢儴鍒嗕互杩涜纾烽吀鍖栫瓑杩囩▼銆?/p>

鍐呭惈瀛?鏋勬垚鍩哄洜缁勭殑闈炵紪鐮侀儴鍒? 涓殑鍩哄簭閫氬父鏄喅瀹氬熀鍥犺〃杈鹃噺鍜岃泲鐧借川缁撳悎浣嶇偣鐨勮皟鎺у簭鍒椼€?/p>

satellite DNA 鏄潃涓濈矑鍜屽紓鏌撹壊璐ㄧ殑涓昏鎴愬垎锛屾槸鍩哄洜缁?junk 閮ㄥ垎涓彂鐜扮殑鍩哄簭鐨勪竴涓緥瀛愩€?/p>

搴忓垪鍩哄簭涓庝竴鑷存€у簭鍒?/h1>

搴忓垪鍩哄簭鐨勪笉鍚屽嚭鐜板彲鑳藉郊姝や笉鍚岋紝鍗充娇瀹冧滑鎵ц鐩稿悓鐨勫姛鑳姐€傚洜姝わ紝鎴戜滑瀹氫箟浜嗕竴缁勫簭鍒楃殑涓€鑷存€у簭鍒椼€?/p>

缁欏畾涓€缁勫簭鍒楋紝涓€鑷村簭鍒楋紙涔熺О涓烘爣鍑嗗簭鍒楋級鏄€氳繃鍦ㄦ瘡涓綅缃彁鍙栨渶甯歌鐨勬牳閰?姘ㄥ熀閰告畫鍩鸿€岃幏寰楃殑搴忓垪銆?/p>

渚嬪锛孉GAT銆乀GAC鍜孉CAC鐨勪竴鑷村簭鍒楁槸AGAC銆?/p>

灏嗗簭鍒椾竴涓帴涓€涓湴鍐欏湪鍙︿竴涓笅闈㈠彲浠ユ洿瀹规槗鍦扮湅鍒拌繖涓€鐐癸紙A鏄綅缃?涓渶甯歌鐨勬畫鍩猴紝G鏄綅缃?涓渶甯歌鐨勬畫鍩猴紝渚濇绫绘帹锛夈€?/p>

AGAT := Sequence 1TGAC := Sequence 2ACAC := Sequence 3 AGAC := Consensus sequence

鍩哄簭鍜屼竴鑷存€у簭鍒楃殑琛ㄧず

閴翠簬motifs鏄湪澶氫釜浣嶇疆鍙戠幇鐨勫瓙涓叉ā寮忥紝姣忎釜浣嶇疆鍙兘鏈変篃鍙兘娌℃湁绐佸彉锛屽洜姝ゅ瓨鍦ㄨ〃绀鸿繖浜涘簭鍒楃殑鐗瑰畾鏂瑰紡銆?/p>

鏂囨湰琛ㄧず

鎴戜滑灏嗕娇鐢ㄤ互涓嬫牳閰稿簭鍒楃ず渚嬫潵浠嬬粛琛ㄧず鐨勫悇涓柟闈€備緥瀛愶紝

T [GA] N Y {T} [CT] R

鍦ㄦ琛ㄧず涓紝A銆乀銆丟 鍜?C 琛ㄧず鍥涚鍙兘鐨勬牳鑻烽吀纰卞熀锛氳吅鍢屽懁銆佽兏鑵哄槯鍟躲€佽優鍢у暥鍜岄笩鍢屽懁銆?/span>N 琛ㄧず浠讳綍鍚爱纰卞熀锛?/span>Y 鍜?R 鍒嗗埆琛ㄧず鍢у暥锛圱鎴朇锛夊拰鍢屽懁锛圓鎴朑锛夈€?/span>[GA] 鎰忓懗鐫€锛屽湪閭ｄ釜浣嶇疆锛岃涔堟槸 G锛岃涔堟槸 A銆?/span>

鍩哄簭鎼滃闂

鎵€璋?鍩哄簭鎼滃闂(Motif finding) 鏄寚鍦ㄧ敓鐗╀綋DNA搴忓垪褰撲腑瀵绘壘鏈夐噸瑕佸姛鑳界殑鍩哄洜鐗囨锛岃繖浜涚墖娈靛湪鐢熺墿鐨勬紨鍖栬繃绋嬩腑琚繚鐣欎簡涓嬫潵锛岀敓鐗╀綋涓殑纰卞熀瀵归珮杈炬暟浜夸釜锛屽浣曞湪浼楀搴忓垪涓壘鍑轰竴娈甸噸瑕佷笖鏈夋剰涔夌殑鍩哄洜搴忓垪锛屼究鎴愪负浜嗕竴涓噸瑕佺殑闂銆?/p>

鍦ㄨ绠椾笂锛?em>Motif finding鍙互瀹氫箟涓猴細

缁欏畾T 鏉￠暱搴︿负 N 鐨勫簭鍒楋紝鎵惧埌鍑虹幇鍦ㄦ瘡T涓簭鍒椾腑鐨勯暱搴︿负L鐨勬渶浣虫ā寮忋€?/p>

涓嶅悓绫诲瀷鐨勫緱鍒嗗彲浠ュ府鍔╂垜浠缁欏畾鐨勬ā寮忚繘琛岃瘎鍒嗭紝骞堕€夋嫨鏈€浣崇殑妯″紡銆?/p>

瀵逛簬涓嬮潰鐨勪緥瀛愶紝鎴戜滑灏嗚€冭檻 T = 5銆丯 = 100 鍜?L = 8銆備篃灏辨槸璇达紝鎴戜滑鏈?5 涓暱搴︿负 100 鐨勫簭鍒楋紝鎴戜滑甯屾湜浠庢瘡涓簭鍒椾腑鎵惧埌涓€涓暱搴︿负 8 鐨勫簭鍒楀熀搴忥紝浣垮緱杩欎簺鍩哄簭褰兼鐩镐技銆?/p>

Motif 鍊欓€夌粨鏋滆瘎鍒?/h1>

棣栧厛锛屾垜浠皢鐪嬪埌濡備綍涓虹粰瀹氱殑涓€缁?motifs 璇勫垎銆?/p>

涔熷氨鏄锛屾垜浠亣璁炬垜浠粠姣忎釜 T 搴忓垪涓緱鍒颁竴浜涢暱搴︿负 L 鐨勫簭鍒楋紝杩欎簺搴忓垪鏄垜浠殑 motif candidates 銆?/p>

閴翠簬姝わ紝鎴戜滑灏嗙湅鍒板浣曞杩欎簺鍊欓€変富棰樿繘琛岃瘎鍒嗐€傚湪涓嬩竴鑺備腑锛屾垜浠皢鐪嬪埌濡備綍鍦ㄥ師濮嬪簭鍒椾腑鎵惧埌鍩哄簭銆?/p>

鍋囪鎴戜滑鏈変互涓嬩粠涓€缁勫簭鍒椾腑鑾峰緱鐨勫€欓€夊熀搴忥紙5 涓?motif candidates 锛屾瘡涓暱搴︿负 8锛夈€?/p>

Alignment	A G G T A C T T
	C C A T A C G T
	A C G T T A G T
	A C G T C C A T
	C C G T A C G G

5 motifs 锛屾瘡涓暱搴︿负8銆傜孩鑹插瓧姣嶈〃绀哄亸绂诲叡璇?deviation from consensus)

浠庣粰瀹氱殑鍩哄簭涓紝鎴戜滑棣栧厛鏋勫缓涓€涓?profile matrix 锛屽畠鍙槸姣忎釜浣嶇疆姣忎釜鏍歌嫹閰哥⒈鍩虹殑棰戠巼銆?/p>

鍥犳锛屽浜庢垜浠笂闈㈢殑绀轰緥锛屼互涓嬫槸鎴戜滑鐨勯厤缃?profile matrix 鐨勬牱瀛愶紝

Profile	A	3 0 1 0 3 1 1 0
	G	2 4 0 0 1 4 0 0
	C	0 1 4 0 0 0 3 1
	T	0 0 0 5 1 0 1 4

姣忎竴鍒椾腑鏈€甯歌鐨勫瓧姣嶇粍鍚堝湪涓€璧凤紝涓烘垜浠彁渚涗簡鍏辫瘑瀛楃涓层€傚洜姝わ紝鍦ㄦ湰渚嬩腑锛屾垜浠殑涓€鑷存€у簭鍒楀湪绗竴涓綅缃湁A锛屽洜涓哄畠鍦ㄧ1鍒椾腑鍑虹幇鐨勬鏁版渶澶氾紝绫讳技鍦帮紝鎴戜滑灏嗗湪绗簩涓綅缃湁C锛屼緷姝ょ被鎺紝浠ヨ幏寰椾互涓嬩竴鑷存€у簭鍒楋細ACGTACGT銆?/span>

杩欑粍 motif candidates 鐨勪竴涓彲鑳藉緱鍒嗘槸绐佸彉鎬绘暟锛堝湪涓婇潰鐨勪緥瀛愪腑锛屽嵆2+1+1+0+2+1+2+1=10锛夈€傛垜浠殑鐩爣鏄敖閲忓噺灏戣繖涓垎鏁般€?/p>

鏇村悎閫傜殑鍒嗘暟鏄?profile matrix 鐨勭喌(entropy)銆?/p>

鐔?entropy)鏄　閲忔瘡涓綅缃畧鎭掔▼搴︾殑鎸囨爣銆傞珮鐔垫剰鍛崇潃浣庡畧鎭掞紝浣庣喌鎰忓懗鐫€楂樺畧鎭掋€傝 prob(R锛宭) 涓哄墿浣橰鍑虹幇鍦ㄤ綅缃甽鐨勬鐜囷紝鍗?prob(R, l) = count(R, l) / T 銆?/p>

渚嬪锛屽浜庣粰瀹氱殑涓婅堪 profile matrix 锛?prob锛圕锛?锛?2/5 銆?/p>

鎴戜滑灏嗗垎鍒祴閲忔瘡涓綅缃殑鐔点€傚叾瀹氫箟濡備笅锛?/p>

prob (R,l) log prob (R,l)

涔熷氨鏄锛屾垜浠鎵€鏈変綅缃殑鎵€鏈夋畫鐣欑墿鐨?prob(R,l)log(prob(R,l)) 姹傚拰銆?/p>

瀵绘壘鍩哄簭锛堥殢鏈虹畻娉曪級

鎴戜滑灏嗕娇鐢ㄤ竴绉嶉殢鏈鸿凯浠ｇ畻娉曟潵瀵绘壘 motifs 銆傛垜浠娇鐢ㄩ殢鏈鸿凯浠ｇ畻娉曪紝鍥犱负灏濊瘯 profile matrix鐨勬墍鏈夊彲鑳藉€兼槸涓嶅彲琛岀殑銆?/p>

褰撹瘎鍒嗗嚱鏁颁粎浣跨敤涓€鑷存€у簭鍒楄€屼笉鏄?profile matrix 鏃讹紝鏈夋洿蹇殑绠楁硶锛屼絾鐔靛嚱鏁版槸涓€涓瘮绾补鍩轰簬涓€鑷存€у簭鍒楃殑璇勫垎鍑芥暟鏇村ソ鐨勮瘎鍒嗗嚱鏁帮紝瀹冧笉鑰冭檻涓€鑷存€у簭鍒楃殑姣忎釜浣嶇疆鐨勪繚瀹堟€с€?/p>

1. 鍦ㄦ瘡涓粰瀹氬簭鍒椾腑闅忔満閫夋嫨鍒濆 motifs 銆傝繖缁欎簡鎴戜滑涓€缁勫€欓€?motifs M銆?/li>
2. 璁＄畻 motifs 鍊欓€塎鐨?profile matrix P锛堝鍓嶄竴鑺傛墍杩帮級銆?/li>
3. 瀵逛簬姣忎釜搴忓垪 S锛岀粰瀹氶厤缃?profile matrix P锛屾壘鍒版渶浣崇殑 motifs 锛堜笅闈㈡湁鏇磋缁嗙殑鎻忚堪锛夈€傝繖涓烘垜浠彁渚涗簡涓€缁勬柊鐨?motifs 鍊欓€?M銆?/li>
4. 濡傛灉鏂扮殑鍊欓€?motifs 闆嗕笌鍓嶄竴缁勪笉鍚岋紝鍒欒繑鍥炲埌 2銆傚惁鍒欏仠姝€?/li>

瀵逛簬绗?3 姝ワ紝鎴戜滑鍙互瀵圭粰瀹氱殑閰嶇疆 profile matrix P 鐨勬瘡涓?L-mer 杩涜璇勫垎銆傝瘎鍒嗗涓嬶細

log prob (R,l)

鍏朵腑 sum 鍦?motifs 鐨勬畫鍩轰笂锛岃€?prob 鐢辫疆寤撶煩闃靛畾涔夈€備緥濡傦紝瀵逛簬搴忓垪 ACAGACAT锛屽垎鏁板皢涓?-[log(prob(A, 1)) + log(prob(C, 2)) + log(prob(A, 3)) + … + log( 姒傜巼锛圱锛?锛夛級]銆?/p>

鍏朵腑 sum 瓒呰繃 motifs 鐨勬畫鍩猴紝 prob 鐢?profile matrix 瀹氫箟銆?/p>

渚嬪锛屽浜庡簭鍒?span style=”font-size: 15px;”>ACAGACAT锛屽垎鏁板皢涓?/p>

[log(prob(A,1)) + log(prob(C,2)) + log(prob(A,3)) + 鈥?+ log(prob(T,8))]

闅忔満绠楁硶鏀舵暃閫熷害闈炲父蹇€傜敱浜庢垜浠殑鏈€缁堢粨鏋滃彇鍐充簬寮€濮嬫椂杩涜鐨勯殢鏈哄垵濮嬪寲锛屽洜姝ゆ垜浠€氬父澶氭杩愯鏁翠釜杩囩▼锛屽苟浠庢墍鏈夎繍琛屼腑閫夋嫨鐔垫渶浣庣殑motif闆?/p>

鍚夊竷鏂噰鏍风畻娉?/h1>

瀵逛笂杩伴殢鏈虹畻娉曠◢浣滀慨鏀癸紝浣胯绠楁硶鐨勬€ц兘鏇村姞鍑鸿壊銆傝繖涓増鏈绉颁负 Gibb's Sampler 绠楁硶銆?/p>

鎵ц Gibb 閲囨牱鐨勭▼搴忥紙涓庝互鍓嶇畻娉曠殑涓昏鍙樺寲浠ョ矖浣撴樉绀猴級锛?/p>

瀵逛笂杩伴殢鏈虹畻娉曠◢浣滀慨鏀癸紝浣胯绠楁硶鐨勬€ц兘鏇村姞鍑鸿壊銆傝繖涓増鏈绉颁负 鍚夊竷鏂噰鏍风畻娉?Gibb鈥檚 Sampling Algorithm)

鎵ц鍚夊竷鏂噰鏍风殑绋嬪簭锛堜笌浠ュ墠绠楁硶鐨勪富瑕佸彉鍖栦互绮椾綋鏄剧ず锛夛細

1. 闅忔満閫夋嫨姣忎釜缁欏畾鐨?T 搴忓垪鐨勮捣濮嬩綅缃拰鍩哄簭L-mers銆?/li>
2. T 搴忓垪涓?strong>闅忔満閫夋嫨涓€涓?/strong>銆?/li>
3. 涓哄墿浣欑殑 T-1 搴忓垪鍒涘缓 profile matrix 銆?/li>
4. 瀵逛簬绉婚櫎搴忓垪涓殑姣忎釜浣嶇疆锛屾牴鎹?profile matrix 璁＄畻姣忎釜 L-mer 鐨勫垎鏁般€?/li>
5. 浠庤搴忓垪涓彇鏍疯浣跨敤鐨勬柊 L-mer 銆傛瘡涓?L-mer 鐨勯噰鏍锋潈閲嶄负 escore 銆傦紙鎴戜滑浣跨敤 escore 锛屽洜涓哄垎鏁版槸瀵规暟姒傜巼(log probability)锛夈€?/li>
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