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Microbes & Immunity                                               Big data and DNN-based DTI model in CHP



            profile of 1, indicating that the bindings of TFs, miRNAs,   miRNAs binding to the n-th lncRNA. e [i], f [i], and g [i],
                                                                                                          z
                                                                                                   y
                                                                                               x
            lncRNAs, and RNA polymerase to the l-th target gene still   respectively, denote the expression levels of the x-th TF, the
            exist. The expression level of the  l-th gene results from   y-th lncRNA, and the z-th miRNA in the i-th sample. o
                                                                                                            mx
            transcriptional regulations of TFs and lncRNAs, the post-  denotes the transcriptional regulatory ability of the x-th
            transcriptional regulations of miRNAs, and the basal level   TF on the  n-th lncRNA.  ρ  denotes the transcriptional
                                                                                     ny
            of the l-th gene with measurement noise in Equation II.   regulatory ability of the y-th lncRNA on the n-th lncRNA.
            Furthermore, the transcriptional regulations of TFs and   τ  > 0 represents the post-transcriptional regulatory
                                                                nz
            lncRNAs, the post-transcriptional regulations of miRNAs,   ability of the z-th miRNA and the n-th lncRNA. N is the
            and basal expression level (RNA polymerase binding) can   total amount of lncRNAs in the candidate GWGEN, and
            be influenced by DNA methylation in Equation III.  I is the total amount of data samples (fibrosis slice cells
              In addition, the miRNA regulatory system model of   or non-fibrosis slice cells).  u  represents the basal level,
                                                                                       n
            candidate GRN, describing the transcriptional expression   that is, the change in expression of the n-th lncRNA due
            of the  m-th miRNA of lung slice cells for sample  i, is   to phosphorylation, ubiquitination, and acetylation. ν [i]
                                                                                                           n
            constructed by Equation IV:                        represents the random noise in the i-th sample due to the
                                                               residuals of modeling and measurement noise.
                  X m
                                     Z m
                            Y m
                      ei[]+
            di[]= ∑ η mx x  ∑ κ my fi[]− ∑ λ mz gi di[] []+ c ++ hi[]  2.4. System identification and order detection
             m
                                 y
                                                       m
                                                   m
                                           z
                                              m
                  x=1      y=1       z=1                       in stochastic regression models for real gene
            for m = 1,2,…,M and i=1,2,…,I              (IV)    regulation network of candidate genome-wide and
                                                               EINs
              where d [i] represents the expression level of the m-th
                     m
            miRNA in the  i-th sample.  X ,  Y , and  Z , respectively,   After constructing the protein interaction regression model
                                    m
                                       m
                                              m
            represent the total numbers of TFs, lncRNAs, and   for candidate PPINs in Equation I and the regulatory
            miRNAs binding to the m-th miRNA. e [i], f [i], and g [i],   models of genes/miRNAs/lncRNAs for candidate GRNs in
                                                y
                                            x
                                                       z
            respectively, denote the expression levels of the x-th TF, the   Equations II, IV, and V, we applied system identification
                                                                                                   19
                                                                     17
            y-th lncRNA, and the z-th miRNA in the i-th sample. η    method  and system order detection scheme  to identify
                                                         mx
            denotes the transcriptional regulatory ability of the x-th   protein interactions in the protein interaction model in
            TF on the  m-th miRNA.  k  denotes the transcriptional   Equation I and genetic regulations of genetic regulation
                                  my
            regulatory ability of the y-th lncRNA on the m-th miRNA.   models in Equations II, IV, and V. Using parameters a , β
                                                                                                          kw
                                                                                                             k
            λ  > 0 represents the post-transcriptional regulatory ability   for the protein interaction model and δ , k , and τ  for the
                                                                                              lx
                                                                                                my
                                                                                                       nz
             mz
            of the z-th miRNA in degrading the m-th miRNA. M is the   gene/miRNA/lncRNA regulatory models, we combined
            total amount of miRNAs in the candidate GWGEN, and I   lncRNA expression data and DNA phosphorylation,
            is the total number of data samples (fibrosis slice cells or   ubiquitination, and methylation of each lung slice cell
            non-fibrosis slice cells). c  represents the basal level due to   with the protein interaction model and the gene/miRNA/
                                m
            phosphorylation, ubiquitination, acetylation, or other gene   lncRNA regulatory models to identify real GWGENs of
            regulatory effects that are considered to have unknown   CHP and non-CHP using their microarray data. Next, our
            effects on the miRNA. h [i] represents the random noise   goal was to use system identification and order detection
                                m
            of the m-th miRNA in the i-th sample due to the residuals   methods to filter out false-positive interactions and
                                                                        17
            from model establishment and experimental measurement   regulations  from the candidate GWGENs. In addition,
            noise.                                             Equations II, IV, and V can be represented as the following
                                                               linear regression equations (Equations VI-IX) to obtain
              Furthermore, the lncRNA regulatory system model of   the parameter vectors for protein interactions and gene
            candidate GRN, describing the transcriptional expression   regulations in candidate GWGEN of CHP and non-CHP. 18
            level of the  n-th lncRNA of lung cells for sample  i, is
            presented in Equation V:                                                                    a a   
                                                                                                         k1 
                  X n      Y n       Z n                                                                a k2 
            qi[]= ∑ oe i[]+ ∑ ρ ny  f i[]− ∑ τ nz g iq i[] []+  u ++ vi[]  Si   =  Si Si Si Si    Si S   i    ×1     
                                                                                            
                                                                         
                                                                                  
                                                                              
                                                                                           k  
                                y
                                          z
             n
                    nx x
                                                      n
                                                                k  
                                                  n
                                             n
                  x=1      y=1       z=1                                k   1    k   2    Kk       
                                                                                                        a Kk 
            for n = 1,2,…,N and i=1,2,…,I              (V)                                                
                                                                                                        b k 
              where q [i] represents the expression level of the n-th   +ϕ  i   =σ  i   β*  +ϕ  i  
                     n
            lncRNA  in  the  i-th  sample.  X ,  Y ,  and  Z ,  respectively,   k    k    k  k  
                                     n
                                        n
                                               n
            represent the total amount of TFs,  lncRNAs, and   for k = 1,2,…,K and i=1,2,…,I              (VI)
            Volume 2 Issue 2 (2025)                         81                               doi: 10.36922/mi.4620
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