A mixture model-based discriminate analysis for identifying ordered transcription factor binding site pairs in gene promoters directly regulated by estrogen receptor-alpha.
BACKGROUND
To detect and select patterns of transcription factor binding sites (TFBSs) which distinguish genes directly regulated by estrogen receptor-alpha (ERalpha), we developed an innovative mixture model-based discriminate analysis for identifying ordered TFBS pairs.


RESULTS
Biologically, our proposed new algorithm clearly suggests that TFBSs are not randomly distributed within ERalpha target promoters (P-value < 0.001). The up-regulated targets significantly (P-value < 0.01) possess TFBS pairs, (DBP, MYC), (DBP, MYC/MAX heterodimer), (DBP, USF2) and (DBP, MYOGENIN); and down-regulated ERalpha target genes significantly (P-value < 0.01) possess TFBS pairs, such as (DBP, c-ETS1-68), (DBP, USF2) and (DBP, MYOGENIN). Statistically, our proposed mixture model-based discriminate analysis can simultaneously perform TFBS pattern recognition, TFBS pattern selection, and target class prediction; such integrative power cannot be achieved by current methods.


BACKGROUND
The software is available on request from the authors.


BACKGROUND
lali@iupui.edu


BACKGROUND
Supplementary data are available at Bioinformatics online.
Li
Lang
L
Division of Biostatistics, Department of Medicine, Indiana University School of Medicine Indianapolis, IN 47405, USA. lali@iupui.edu
Cheng
Alfred S L
AS
Jin
Victor X
VX
Paik
Henry H
HH
Fan
Meiyun
M
Li
Xiaoman
X
Zhang
Wei
W
Robarge
Jason
J
Balch
Curtis
C
Davuluri
Ramana V
RV
Kim
Sun
S
Huang
Tim H-M
TH
Nephew
Kenneth P
KP
D000465:Algorithms; D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D003198:Computer Simulation; D016002:Discriminant Analysis; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D008956:Models, Chemical; D008957:Models, Genetic; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D047628:Estrogen Receptor alpha; D014157:Transcription Factors