ANALYSIS AND PREDICTION OF TRAUMATIC BRAIN INJURY AND CONCUSION SYMPTOMSProvided are methods for detecting or diagnosing a traumatic brain injury or TBI by detecting concentration levels miRNAs associated with TBI in saliva. Methods for controlled and normalized comparisons of salivary miRNA concentration levels are further provided. Assay kits comprising salivary miRNAs, probes and/or primers for detecting salivary miRNAs are also provided.A method for detecting or diagnosing a concussion, mild traumatic brain injury ('mTBI'), or other traumatic brain injury ('TBI') comprising:(a) determining abundance or concentration level(s) of one or more micro RNAs ('miRNAs') in a saliva sample taken from a human subject, and(b) comparing the determined abundance or concentration level(s) of the one or more miRNAs against normal level(s) of the same one or more miRNAs, wherein the normal (or control) level is that found in a subject, or an average from two of more subjects, not having a concussion, mild traumatic brain injury; or abundance or concentration level(s) determined in the subject prior to an event that could produce a concussion, mTBI or other TBI, and(c) selecting a subject having an abnormal level of said one or more miRNAs as having, or as being at higher risk for having, a concussion, mild traumatic brain injury ('mTBI') or other traumatic brain injury ('TBI');wherein the one or more miRNAis selected from the group consisting hsa-let-7f-5p, hsa-let-7i, hsa-miR- 10a-5p, hsa-miR- 10b-5p, hsa-miR-23a-3p, hsa-mir-23b, hsa-mir-25, hsa- miR-25-3p, hsa-mir-26a-l, hsa-mir-26a-2, hsa-miR-26a-5p, hsa-mir-26b, hsa-miR-26b-5p, hsa-mir-28, hsa-miR-28-3p, hsa-miR-28-5p, hsa-miR-29c-3p, hsa-mir-30b, hsa-miR-30e-3p, hsa-miR-30e-5p, hsa-mir-92a-l, hsa-mir-92a-2, hsa-mir-103a-l, hsa-mir-103a-2, hsa-miR- 125b-l-3p, hsa-miR-125b-2-3p, hsa-miR-141-3p, hsa-miR-148b-3p, hsa-mir-151a, hsa-miR- 151a-3p, hsa-miR-151a-5p, hsa-miR-155-5p, hsa-mir-181a-2, hsa-miR-181a-5p, hsa-miR- 182-5p, hsa-miR- 193 a-3p, hsa-miR-203a-3p, hsa-miR-205-5p, hsa-mir-218-2, hsa-miR-221- 3p, hsa-miR-320c, hsa-miR-338-3p, hsa-miR-338-5p, hsa-miR-342-5p, hsa-miR-374a-5p, hsa-miR-378d, hsa-miR-378f, hsa-miR-378g, hsa-miR-378i, hsa-miR-454-3p, hsa-miR-501- 3p, hsa-miR-532-5p, hsa-miR-577, hsa-miR-625-3p, hsa-miR-744-5p, hsa-miR-944, hsa- miR-1273g-5p, hsa-miR-1285-3p, hsa-miR-1303, hsa-miR-1307-3p, hsa-miR-3074-5p, hsa- mir-3160-1, hsa-mir-3613, hsa-miR-3613-5p, hsa-miR-3916, hsa-mir-4532, hsa-mir-5091, hsa-miR-6770-5p and those miRNA which share the seed sequences as the above listed miRNAs; and/or are selected from the group consisting of at least one of miR-769, miR-769- 3p, miR-769-5p, miR-320c-l, miR-320c-l-3p, miR-320c-l-5p, miR-4792, miR-4792-3p, miR-4792-5p, miR-140, miR-140-3p, miR-140-5p, miR-629, miR-629-3p, miR-629-5p, miR-192, miR-192-3p, miR-192-5p, miR-145, miR-145-3p, miR-145-5p, let-7a, let-7a-3p, let-7s-5p, miR-133a, miR-133a-3p, miR-133a-5p, miR-1307, miR-1307-3p, miR-1307-5p, miR-200b, miR-200b-3p, miR-200b-5p, let-7a, let-7a-3p, let-7a-5p, miR-4508, miR-4508-3p, miR-4508-5p, miR-30e, miR-30e-3p, miR-30e-5p, let-7b, let-7b-3p, let-7b-5p, miR-194, miR-194-3p, miR-194-5p, miR-199a, miR-199a-3p, miR-199a-5p, let-7f, let-7f-3p, let-7f-5p, miR-128, miR-128-3p, miR-128-5p, miR-215, miR-215-3p, miR-215-5p, miR-149, miR- 149-3p, miR-149-5p, miR-421, miR-421-3p, and miR-421-5p; and those miRNA which share the seed sequences as the above listed miRNAs.
외상성 뇌 손상 및 뇌진탕 증상의 분석 및 예측본 발명은 타액 중에서 TBI와 연관된 miRNA 농도 수준을 검출함으로써 외상성 뇌 손상 또는 TBI를 검출하거나 진단하기 위한 방법에 관한 것이다. 타액 miRNA 농도 수준의 제어된 그리고 정규화된 비교를 위한 방법을 추가로 제공한다. 타액 miRNA, 타액 miRNA를 검출하기 위한 프로브 및/또는 프라이머를 포함하는 어세이 키트가 또한 제공된다.뇌진탕, 경증의 외상성 뇌 손상(mild traumatic brain injury: mTBI) 또는 기타 외상성 뇌 손상(traumatic brain injury: TBI)의 검출 또는 진단 방법으로서,(a) 인간 대상체로부터 취한 타액 샘플 중의 하나 이상의 마이크로 RNA(micro RNA: miRNA)의 존재비 또는 농도 수준을 결정하는 단계;(b) 상기 하나 이상의 miRNA의 상기 결정된 존재비 또는 농도 수준을 동일한 하나 이상의 miRNA의 정상 수준과 비교하는 단계로서, 상기 정상(또는 대조군) 수준이 대상체에서 발견된 것, 또는 뇌진탕, 경증의 외상성 뇌 손상을 갖지 않는 2명 이상의 대상체로부터의 평균; 또는 뇌진탕, mTBI 또는 기타 TBI를 일으킬 수 있었던 사건 전에 상기 대상체에서 결정된 존재비 또는 농도 수준인, 단계; 및(c) 뇌진탕, 경증의 외상성 뇌 손상(mTBI) 또는 기타 외상성 뇌 손상(TBI)을 갖거나 가질 더 높은 위험에 있는 상기 하나 이상의 miRNA의 비정상 수준을 갖는 대상체를 선택하는 단계를 포함하되,상기 하나 이상의 miRNA가 hsa-let-7f-5p, hsa-let-7i, hsa-miR-10a-5p, hsa-miR-10b-5p, hsa-miR-23a-3p, hsa-mir-23b, hsa-mir-25, hsa-miR-25-3p, hsa-mir-26a-1, hsa-mir-26a-2, hsa-miR-26a-5p, hsa-mir-26b, hsa-miR-26b-5p, hsa-mir-28, hsa-miR-28-3p, hsa-miR-28-5p, hsa-miR-29c-3p, hsa-mir-30b, hsa-miR-30e-3p, hsa-miR-30e-5p, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-103a-1, hsa-mir-103a-2, hsa-miR-125b-1-3p, hsa-miR-125b-2-3p, hsa-miR-141-3p, hsa-miR-148b-3p, hsa-mir-151a, hsa-miR-151a-3p, hsa-miR-151a-5p, hsa-miR-155-5p, hsa-mir-181a-2, hsa-miR-181a-5p, hsa-miR-182-5p, hsa-miR-193a-3p, hsa-miR-203a-3p, hsa-miR-205-5p, hsa-mir-218-2, hsa-miR-221-3p, hsa-miR-320c, hsa-miR-338-3p, hsa-miR-338-5p, hsa-miR-342-5p, hsa-miR-374a-5p, hsa-miR-378d, hsa-miR-378f, hsa-miR-378g, hsa-miR-378i, hsa-miR-454-3p, hsa-miR-501-3p, hsa-miR-532-5p, hsa-miR-577, hsa-miR-625-3p, hsa-miR-744-5p, hsa-miR-944, hsa-miR-1273g-5p, hsa-miR-1285-3p, hsa-miR-1303, hsa-miR-1307-3p, hsa-miR-3074-5p, hsa-mir-3160-1, hsa-mir-3613, hsa-miR-3613-5p, hsa-miR-3916, hsa-mir-4532, hsa-mir-5091, hsa-miR-6770-5p, 및 상기 열거된 miRNA와 종자 서열을 공유하는 miRNA로 이루어진 군으로부터 선택되고/되거나; miR-769, miR-769-3p, miR-769-5p, miR-320c-1, miR-320c-1-3p, miR-320c-1-5p, miR-4792, miR-4792-3p, miR-4792-5p, miR-140, miR-140-3p, miR-140-5p, miR-629, miR-629-3p, miR-629-5p, miR-192, miR-192-3p, miR-192-5p, miR-145, miR-145-3p, miR-145-5p, let-7a, let-7a-3p, let-7s-5p, miR-133a, miR-133a-3p, miR-133a-5p, miR-1307, miR-1307-3p, miR-1307-5p, miR-200b, miR-200b-3p, miR-200b-5p, let-7a, let-7a-3p, let-7a-5p, miR-4508, miR-4508-3p, miR-4508-5p, miR-30e, miR-30e-3p, miR-30e-5p, let-7b, let-7b-3p, let-7b-5p, miR-194, miR-194-3p, miR-194-5p, miR-199a, miR-199a-3p, miR-199a-5p, let-7f, let-7f-3p, let-7f-5p, miR-128, miR-128-3p, miR-128-5p, miR-215, miR-215-3p, miR-215-5p, miR-149, miR-149-3p, miR-149-5p, miR-421, miR-421-3p, miR-421-5p, 및 상기 열거된 miRNA와 종자 서열을 공유하는 miRNA 중 1종 이상으로 이루어진 군으로부터 선택되는, 뇌진탕, mTBI 또는 기타 TBI의 검출 또는 진단 방법.