Reads are randomly generated by the K genomes, then the probability

Reads are randomly generated by the K genomes, then the probability that a read xj is 15900046 generated by genome i is Ri . Even if a read xj is generated from genome i, it is possible that the match is not 100 identical due to sequencing errors, alignment errors, and/or single Gracillin site nucleotide polymorphism (SNP). Let p denote the probability of observing a mismatched base pair, then 1- p is the probability of observing a matched base pair. The probability that a read xj is generated by genome i with Mji matched base pairs and Lj {Mji mismatched base pairs is Ri pLj {Mji (1{p)Mji , where Lj maxfLji ,i 1, ???,Kg is the maximum alignment length. Then the probability of observing a read xj in the dataset isK Xh iPr (xj )i Ri pLj {Mji (1{p)Mji :Assuming that the reads are independent of each other, the likelihood function of the data is:Taxonomic Assignment of Metagenomic Reads`(p,R1 , ???,RK ) P Pr (xj )j 1 nn(Lj {Mji(PK Xh ijRi p(1{p)Mjii) ,??R(tz1)arg max Q(hDh ) arg maxR n 1 X (t) T n j 1 ji R(t)K X i” ( log Ri )n X j#)(t) Tji:where the values of Lj and Mji are observable, and the parameters p and Ri 1,2,:::,K ?are to be estimated.This gives Ri(tz1)(i 1,2, ???,K):EM AlgorithmFor this mixture model, the expectation maximization (EM) algorithm [17] is used to calculate the maximum likelihood estimation for the parameters p and Ri 1,2,:::,K ? Let Z (Z1 , ???,Zn ) be the latent variables that determine the genome from which each read originate. The aim is to estimate the unknown parameters h (p,R), where R (R1 , ???,RK ). The likelihood function can be written as: ( ) K i Xh Lj {Mji Mji `(h,M,Z) P I(zj i)Ri p (1{p)n j 1 iThe probability of observing a mismatched base pair is estimated as:n K PP (t) Mji Tji (t) Lj Tjip(tz1)1{j 1 i 1 n K PPj 1 iNIteration step. Repeat the E-step and the M-step until all the parameters converge, i.e., Dp(tz1) {p(t) Dve and DR(tz1) {R(t) D i i ve for i 1,2, ???,K and for some pre-specified small number of e.where I is an indicator function. As the density function is an exponential family function, the likelihood function can be expressed as:`(h,M,Z) ( ) n K XX??exp I(zj i) og (Ri ){Mji log (p=(1{p))zLj log pj 1 iThe estimates of Ri (i 1,2, ???,K) reflect the proportion of reads generated from each of the K candidate genomes. If Ri = 0, then the corresponding genome i is not contained in the sample. If we observe an inequality Ri wRi0 for two genomes i and i0 , then we conclude that the sample contains more reads generated from genomeithan genome i0 . CASIN web However the values of Ri do not give information on which reads are generated by which genomes. Next we show how to assign reads to the K candidate genomes and the taxonomy tree.Taxonomic Assignment of ReadsN NInitialization step. Initialize the values of p andRi (i 1,2, ???,K), call them p(0) and R(0) : For instance, let i the reads be equally distributed among the K genomes, i.e., R(0) 1=K, and let p(0) 0:05: i E-step. Assuming the current estimate of the parameter is h(t) , then the conditional distribution of Zj is:To assign each read to the taxonomic tree, we first estimate how likely it is generated by a specific genome. The probability that read xj is generated by genome i is estimated by. Ri pLj {Mji (1{p)MjiK P nPji :Rn pLj {Mjv (1{p)Mjv(t) Tji : Pr (zj iDM; h(t) )R(t) (p(t) )Lj {Mji (1{p(t) )Mji iK P n:??R(t) (p(t) )Lj {Mjv (1{p(t) )Mjv nThen the E-step result is: Q(hDh(t) ) E og (`(h,M,Z))n K XX j 1 ifor i 1,2, ???,K and j 1,2, ???,n. Then read xj.Reads are randomly generated by the K genomes, then the probability that a read xj is 15900046 generated by genome i is Ri . Even if a read xj is generated from genome i, it is possible that the match is not 100 identical due to sequencing errors, alignment errors, and/or single nucleotide polymorphism (SNP). Let p denote the probability of observing a mismatched base pair, then 1- p is the probability of observing a matched base pair. The probability that a read xj is generated by genome i with Mji matched base pairs and Lj {Mji mismatched base pairs is Ri pLj {Mji (1{p)Mji , where Lj maxfLji ,i 1, ???,Kg is the maximum alignment length. Then the probability of observing a read xj in the dataset isK Xh iPr (xj )i Ri pLj {Mji (1{p)Mji :Assuming that the reads are independent of each other, the likelihood function of the data is:Taxonomic Assignment of Metagenomic Reads`(p,R1 , ???,RK ) P Pr (xj )j 1 nn(Lj {Mji(PK Xh ijRi p(1{p)Mjii) ,??R(tz1)arg max Q(hDh ) arg maxR n 1 X (t) T n j 1 ji R(t)K X i” ( log Ri )n X j#)(t) Tji:where the values of Lj and Mji are observable, and the parameters p and Ri 1,2,:::,K ?are to be estimated.This gives Ri(tz1)(i 1,2, ???,K):EM AlgorithmFor this mixture model, the expectation maximization (EM) algorithm [17] is used to calculate the maximum likelihood estimation for the parameters p and Ri 1,2,:::,K ? Let Z (Z1 , ???,Zn ) be the latent variables that determine the genome from which each read originate. The aim is to estimate the unknown parameters h (p,R), where R (R1 , ???,RK ). The likelihood function can be written as: ( ) K i Xh Lj {Mji Mji `(h,M,Z) P I(zj i)Ri p (1{p)n j 1 iThe probability of observing a mismatched base pair is estimated as:n K PP (t) Mji Tji (t) Lj Tjip(tz1)1{j 1 i 1 n K PPj 1 iNIteration step. Repeat the E-step and the M-step until all the parameters converge, i.e., Dp(tz1) {p(t) Dve and DR(tz1) {R(t) D i i ve for i 1,2, ???,K and for some pre-specified small number of e.where I is an indicator function. As the density function is an exponential family function, the likelihood function can be expressed as:`(h,M,Z) ( ) n K XX??exp I(zj i) og (Ri ){Mji log (p=(1{p))zLj log pj 1 iThe estimates of Ri (i 1,2, ???,K) reflect the proportion of reads generated from each of the K candidate genomes. If Ri = 0, then the corresponding genome i is not contained in the sample. If we observe an inequality Ri wRi0 for two genomes i and i0 , then we conclude that the sample contains more reads generated from genomeithan genome i0 . However the values of Ri do not give information on which reads are generated by which genomes. Next we show how to assign reads to the K candidate genomes and the taxonomy tree.Taxonomic Assignment of ReadsN NInitialization step. Initialize the values of p andRi (i 1,2, ???,K), call them p(0) and R(0) : For instance, let i the reads be equally distributed among the K genomes, i.e., R(0) 1=K, and let p(0) 0:05: i E-step. Assuming the current estimate of the parameter is h(t) , then the conditional distribution of Zj is:To assign each read to the taxonomic tree, we first estimate how likely it is generated by a specific genome. The probability that read xj is generated by genome i is estimated by. Ri pLj {Mji (1{p)MjiK P nPji :Rn pLj {Mjv (1{p)Mjv(t) Tji : Pr (zj iDM; h(t) )R(t) (p(t) )Lj {Mji (1{p(t) )Mji iK P n:??R(t) (p(t) )Lj {Mjv (1{p(t) )Mjv nThen the E-step result is: Q(hDh(t) ) E og (`(h,M,Z))n K XX j 1 ifor i 1,2, ???,K and j 1,2, ???,n. Then read xj.