[GenABEL-dev] [Genabel-commits] r1286 - pkg/ProbABEL/src

Yurii Aulchenko yurii.aulchenko at gmail.com
Thu Aug 15 15:30:08 CEST 2013


Absolutely - the same staff as with "robust" described in previous mail

with --mmscore, though, I am confident that LRT is a wrong thing to do -
this is a REML-style procedure

Yurii

On Wed, Aug 14, 2013 at 9:08 PM, L.C. Karssen <lennart at karssen.org> wrote:

> Another question related to the LRT-based chi^2 implementation:
>
> Is there a reason why LRT-based chi^2 values would be wrong/nonsense
> when running palinear with the --mscore option?
>
> At the moment there is a big "if( !mmscore )" around the chi^2 section
> that was already in place from the old days when LRT-based chi^2 was in
> ProbABEL (but didn't take missing genotypes into account).
>
> I removed the if() and compared to the Wald statistic, the LRT chi^2
> seems a bit off, but not by much.
>
>
> Thanks for any insights!
>
> Lennart.
>
>
>
> On 14-08-13 10:11, L.C. Karssen wrote:
> > On 13-08-13 17:53, Yurii Aulchenko wrote:
> >> This is a long-awaited-for improvement! - great work!
> >
> > Thanks! As always it was a learning experience. With these larger
> > changes you get to know the code better and better. And learn more
> > statistics along the way :-).
> >
> > I decided to go for LRT instead of the Wald test for two reasons:
> > - LRT is theoretically more superior
> > - I found the equation for the Wald on 2df in the ProbABEL paper, but
> > programming-wise I couldn't get it to work. The coxfit2() function for
> > example says it returns the covariance matrix, but after extracting the
> > sub-matrices I still didn't get answers that were close to the
> > (beta/se_beta)^2 values for the 1df case. So, after spending some time,
> > implementing the LRT while only recalculating the null model in the case
> > of missing genotype data was the quickest.
> >
> > I've also added the LRT-chi^2 for Cox and logistic regression now, as
> > well as R-based consistency checks.
> >
> > I haven't looked at the output when using the score option or the robust
> > option at all yet. Any idea if that will require a lot of additional
> > programming? Various people are waiting for the fixed Cox regression, so
> > I would like to put out a new ProbABEL release ASAP.
> >
> >
> > Thanks,
> >
> > Lennart.
> >
> >
> >>
> >> ----------------------
> >> Yurii Aulchenko
> >> (sent from mobile device)
> >>
> >> On 8 Aug 2013, at 15:19, "noreply at r-forge.r-project.org"
> >> <noreply at r-forge.r-project.org> wrote:
> >>
> >>> Author: lckarssen
> >>> Date: 2013-08-08 13:19:30 +0200 (Thu, 08 Aug 2013)
> >>> New Revision: 1286
> >>>
> >>> Modified:
> >>>   pkg/ProbABEL/src/eigen_mematrix.cpp
> >>>   pkg/ProbABEL/src/eigen_mematrix.h
> >>>   pkg/ProbABEL/src/main.cpp
> >>>   pkg/ProbABEL/src/mematri1.h
> >>>   pkg/ProbABEL/src/mematrix.h
> >>>   pkg/ProbABEL/src/reg1.cpp
> >>>   pkg/ProbABEL/src/regdata.cpp
> >>>   pkg/ProbABEL/src/regdata.h
> >>> Log:
> >>> Added chi^2 information to the ProbABEL output for linear regression.
> >>> NOTE: for palogist and pacoxph this still needs to be fixed!!!
> >>>
> >>> The chi^2 values are based on the LRT. The null model is calculated at
> >>> the beginning (this was already part of ProbABEL for a long time). In
> >>> the case of missing genotype data the null model is recalculated for
> >>> that SNP only. So for people with imputed data there should be no
> >>> difference in computation time.
> >>>
> >>> This is a bit of a rough implementation. Maybe some more work is
> >>> needed to make it better (in terms of programming style/efficiency).
> >>>
> >>> Changes per file:
> >>> src/main.cpp:
> >>> - Some small (unrelated) changes to the way progress information is
> printed
> >>> - Changed output precision of beta, se_beta, chi^2 to 6 instead of 9
> digits
> >>> - around line 700 is where the recalculation of the null model is done.
> >>> src/regdata.h, src/regdata.cpp:
> >>> - Add a function remove_snp_from_X() that removes the genotype data
> >>>   from the design matrix. This is necessary, because in order to know
> >>>   which individuals have missing genotype data (and therefore should
> >>>   be excluded from the null estimation), we first need to have the
> >>>   genotype data in.
> >>> src/reg1.cpp:
> >>> - At the beginning of apply_model() check if we are calculating the
> >>>   null model. if so, we don't need to apply the genotypic model at
> >>>   all.
> >>> src/eigen_mematrix.h, src/eigen_mematrix.cpp:
> >>> - Implement the delete_column() function. When transitioning to Eigen
> >>>   this function wasn't used anywhere in the code, so it wasn't
> >>>   carried over from the mematrix files.
> >>> src/mematri1.h, src/mematrix.h:
> >>> - Set the col/row number argument to const in the delete_column() and
> >>>   delete_row() functions.
> >>>
> >>>
> >>>
> >>>
> >>>
> >>> Modified: pkg/ProbABEL/src/eigen_mematrix.cpp
> >>> ===================================================================
> >>> --- pkg/ProbABEL/src/eigen_mematrix.cpp    2013-08-08 10:07:32 UTC
> (rev 1285)
> >>> +++ pkg/ProbABEL/src/eigen_mematrix.cpp    2013-08-08 11:19:30 UTC
> (rev 1286)
> >>> @@ -362,4 +362,30 @@
> >>>     return temp;
> >>> }
> >>>
> >>> +
> >>> +template<class DT>
> >>> +void mematrix<DT>::delete_column(const int delcol)
> >>> +{
> >>> +    if (delcol > ncol || delcol < 0)
> >>> +    {
> >>> +        fprintf(stderr, "mematrix::delete_column: column out of
> range\n");
> >>> +        exit(1);
> >>> +    }
> >>> +
> >>> +    // Eigen::Matrix<DT,-1,-1,0,-1,-1> *auxdata =
> >>> +    //     new Eigen::Matrix<DT,-1,-1,0,-1,-1>;
> >>> +    MatrixXd auxdata = data;
> >>> +
> >>> +    data.resize(data.rows(), data.cols()-1);
> >>> +
> >>> +    int rightColsSize = auxdata.cols() - delcol - 1;
> >>> +
> >>> +    data.leftCols(delcol) = auxdata.leftCols(delcol);
> >>> +    data.rightCols(rightColsSize) = auxdata.rightCols(rightColsSize);
> >>> +
> >>> +    ncol--;
> >>> +}
> >>> +
> >>> +
> >>> +
> >>> #endif
> >>>
> >>> Modified: pkg/ProbABEL/src/eigen_mematrix.h
> >>> ===================================================================
> >>> --- pkg/ProbABEL/src/eigen_mematrix.h    2013-08-08 10:07:32 UTC (rev
> 1285)
> >>> +++ pkg/ProbABEL/src/eigen_mematrix.h    2013-08-08 11:19:30 UTC (rev
> 1286)
> >>> @@ -37,6 +37,8 @@
> >>>     mematrix operator*(const mematrix &M);
> >>>     mematrix operator*(const mematrix *M);
> >>>
> >>> +    void delete_column(const int delcol);
> >>> +
> >>>     void reinit(int nr, int nc);
> >>>
> >>>     unsigned int getnrow(void)
> >>>
> >>> Modified: pkg/ProbABEL/src/main.cpp
> >>> ===================================================================
> >>> --- pkg/ProbABEL/src/main.cpp    2013-08-08 10:07:32 UTC (rev 1285)
> >>> +++ pkg/ProbABEL/src/main.cpp    2013-08-08 11:19:30 UTC (rev 1286)
> >>> @@ -208,9 +208,9 @@
> >>>                 << input_var.getSep()
> >>>                 << "sebeta_SNP_recA1";
> >>>     *outfile[4] << input_var.getSep()
> >>> -                << "beta_SNP_odom"
> >>> +                << "beta_SNP_odomA1"
> >>>                 << input_var.getSep()
> >>> -                << "sebeta_SNP_odom";
> >>> +                << "sebeta_SNP_odomA1";
> >>>     if (input_var.getInteraction() != 0)
> >>>     {
> >>>         //Han Chen
> >>> @@ -263,7 +263,7 @@
> >>>     *outfile[1] << input_var.getSep() << "chi2_SNP_A1\n";   //
> "loglik\n";
> >>>     *outfile[2] << input_var.getSep() << "chi2_SNP_domA1\n";//
> "loglik\n";
> >>>     *outfile[3] << input_var.getSep() << "chi2_SNP_recA1\n";//
> "loglik\n";
> >>> -    *outfile[4] << input_var.getSep() << "chi2_SNP_odom\n"; //
> "loglik\n";
> >>> +    *outfile[4] << input_var.getSep() << "chi2_SNP_odomA1\n"; //
> "loglik\n";
> >>> }
> >>>
> >>> void create_header2(std::vector<std::ofstream*>& outfile, cmdvars&
> input_var,
> >>> @@ -389,7 +389,7 @@
> >>>
> >>>     masked_matrix invvarmatrix;
> >>>
> >>> -    std::cout << "Reading data ..." << std::flush;
> >>> +    std::cout << "Reading data..." << std::flush;
> >>>     if (input_var.getInverseFilename() != NULL)
> >>>     {
> >>>         loadInvSigma(input_var, phd, invvarmatrix);
> >>> @@ -412,7 +412,7 @@
> >>>                        phd.allmeasured, phd.idnames);
> >>>     }
> >>>
> >>> -    std::cout << " loaded genotypic data ..." << std::flush;
> >>> +    std::cout << " loaded genotypic data..." << std::flush;
> >>>
> >>>     // estimate null model
> >>> #if COXPH
> >>> @@ -421,7 +421,7 @@
> >>>     regdata nrgd = regdata(phd, gtd, -1,
> input_var.isIsInteractionExcluded());
> >>> #endif
> >>>
> >>> -    std::cout << " loaded null data ..." << std::flush;
> >>> +    std::cout << " loaded null data..." << std::flush;
> >>> #if LOGISTIC
> >>>     logistic_reg nrd = logistic_reg(nrgd);
> >>>     nrd.estimate(nrgd, 0, MAXITER, EPS, CHOLTOL, 0,
> >>> @@ -446,14 +446,14 @@
> >>> #endif
> >>>     double null_loglik = nrd.loglik;
> >>>
> >>> -    std::cout << " estimated null model ...";
> >>> +    std::cout << " estimated null model...";
> >>>     // end null
> >>> #if COXPH
> >>>     coxph_data rgd(phd, gtd, 0);
> >>> #else
> >>>     regdata rgd(phd, gtd, 0, input_var.isIsInteractionExcluded());
> >>> #endif
> >>> -    std::cout << " formed regression object ...";
> >>> +    std::cout << " formed regression object...\n";
> >>>
> >>>
> >>>     // Open a vector of files that will be used for output. Depending
> >>> @@ -505,13 +505,16 @@
> >>>     for (int i = 0; i < maxmod; i++)
> >>>     {
> >>>         beta_sebeta.push_back(new std::ostringstream());
> >>> -        beta_sebeta[i]->precision(9);
> >>> +        beta_sebeta[i]->precision(6);
> >>> +        //*beta_sebeta[i] << scientific;
> >>>         //Han Chen
> >>>         covvalue.push_back(new std::ostringstream());
> >>> -        covvalue[i]->precision(9);
> >>> +        covvalue[i]->precision(6);
> >>> +        //*covvalue[i] << scientific;
> >>>         //Oct 26, 2009
> >>>         chi2.push_back(new std::ostringstream());
> >>> -        chi2[i]->precision(9);
> >>> +        chi2[i]->precision(6);
> >>> +        //*chi2[i] << scientific;
> >>>     }
> >>>
> >>>
> >>> @@ -565,10 +568,10 @@
> >>>             poly = 0;
> >>>         }
> >>>
> >>> +        // Write mlinfo information to the output file(s)
> >>>         // Prob data: All models output. One file per model
> >>>         if (input_var.getNgpreds() == 2)
> >>>         {
> >>> -            // Write mlinfo to output:
> >>>             for (unsigned int file = 0; file < outfile.size(); file++)
> >>>             {
> >>>                 write_mlinfo(outfile, file, mli, csnp, input_var,
> >>> @@ -679,7 +682,7 @@
> >>>                 } // END for(pos = start_pos; pos < rd.beta.nrow;
> pos++)
> >>>
> >>>
> >>> -                //calculate chi2
> >>> +                //calculate chi^2
> >>>                 //________________________________
> >>>                 //cout <<  rd.loglik<<" "<<input_var.getNgpreds() <<
> "\n";
> >>>
> >>> @@ -690,23 +693,41 @@
> >>>
> >>>                     if (input_var.getScore() == 0)
> >>>                     {
> >>> +                        double loglik = rd.loglik;
> >>>                         if (gcount != gtd.nids)
> >>>                         {
> >>>                             // If SNP data is missing we didn't
> >>>                             // correctly compute the null likelihood
> >>> -                            *chi2[model] << "NaN";
> >>> +
> >>> +                            // Recalculate null likelihood by
> >>> +                            // stripping the SNP data column(s) from
> >>> +                            // the X matrix in the regression object
> >>> +                            // and run the null model estimation again
> >>> +                            // for this SNP.
> >>> +// BEWARE, ONLY IMPLEMENTED FOR LINEAR REG!!!
> >>> +// TODO LCK
> >>> +#ifdef LINEAR
> >>> +                            regdata new_rgd = rgd;
> >>> +                            new_rgd.remove_snp_from_X();
> >>> +                            linear_reg new_null_rd(new_rgd);
> >>> +                            new_null_rd.estimate(new_rgd, 0, CHOLTOL,
> model,
> >>> +
> input_var.getInteraction(),
> >>> +
> input_var.getNgpreds(),
> >>> +                                                 invvarmatrix,
> >>> +
> input_var.getRobust(), 1);
> >>> +
> >>> +                            *chi2[model] << 2. * (loglik -
> new_null_rd.loglik);
> >>> +#endif
> >>>                         }
> >>>                         else
> >>>                         {
> >>>                             // No missing SNP data, we can compute the
> LRT
> >>> -                            *chi2[model] << 2. * (rd.loglik -
> null_loglik);
> >>> +                            *chi2[model] << 2. * (loglik -
> null_loglik);
> >>>                         }
> >>> -                        //*chi2[model] << rd.loglik;
> >>>                     } else
> >>>                     {
> >>>                         // We want score test output
> >>>                         *chi2[model] << rd.chi2_score;
> >>> -                        //*chi2[model] << "nan";
> >>>                     }
> >>>                 }
> >>>             } // END first part of if(poly); allele not too rare
> >>>
> >>> Modified: pkg/ProbABEL/src/mematri1.h
> >>> ===================================================================
> >>> --- pkg/ProbABEL/src/mematri1.h    2013-08-08 10:07:32 UTC (rev 1285)
> >>> +++ pkg/ProbABEL/src/mematri1.h    2013-08-08 11:19:30 UTC (rev 1286)
> >>> @@ -301,7 +301,7 @@
> >>> }
> >>>
> >>> template<class DT>
> >>> -void mematrix<DT>::delete_column(int delcol)
> >>> +void mematrix<DT>::delete_column(const int delcol)
> >>> {
> >>>     if (delcol > ncol || delcol < 0)
> >>>     {
> >>> @@ -333,7 +333,7 @@
> >>> }
> >>>
> >>> template<class DT>
> >>> -void mematrix<DT>::delete_row(int delrow)
> >>> +void mematrix<DT>::delete_row(const int delrow)
> >>> {
> >>>     if (delrow > nrow || delrow < 0)
> >>>     {
> >>>
> >>> Modified: pkg/ProbABEL/src/mematrix.h
> >>> ===================================================================
> >>> --- pkg/ProbABEL/src/mematrix.h    2013-08-08 10:07:32 UTC (rev 1285)
> >>> +++ pkg/ProbABEL/src/mematrix.h    2013-08-08 11:19:30 UTC (rev 1286)
> >>> @@ -48,8 +48,8 @@
> >>>     void put(DT value, int nr, int nc);
> >>>     DT column_mean(int nc);
> >>>     void print(void);
> >>> -    void delete_column(int delcol);
> >>> -    void delete_row(int delrow);
> >>> +    void delete_column(const int delcol);
> >>> +    void delete_row(const int delrow);
> >>>
> >>> };
> >>>
> >>>
> >>> Modified: pkg/ProbABEL/src/reg1.cpp
> >>> ===================================================================
> >>> --- pkg/ProbABEL/src/reg1.cpp    2013-08-08 10:07:32 UTC (rev 1285)
> >>> +++ pkg/ProbABEL/src/reg1.cpp    2013-08-08 11:19:30 UTC (rev 1286)
> >>> @@ -4,12 +4,22 @@
> >>> mematrix<double> apply_model(mematrix<double>& X, int model, int
> interaction,
> >>>                              int ngpreds, bool is_interaction_excluded,
> >>>                              bool iscox, int nullmodel)
> >>> +// if ngpreds==1 (dose data):
> >>> +// model 0 = additive 1 df
> >>> +// if ngpreds==2 (prob data):
> >>> // model 0 = 2 df
> >>> // model 1 = additive 1 df
> >>> // model 2 = dominant 1 df
> >>> // model 3 = recessive 1 df
> >>> // model 4 = over-dominant 1 df
> >>> {
> >>> +    if(nullmodel)
> >>> +    {
> >>> +        // No need to apply any genotypic model when calculating the
> >>> +        // null model
> >>> +        return (X);
> >>> +    }
> >>> +
> >>>     if (model == 0)
> >>>     {
> >>>         if (interaction != 0 && !nullmodel)
> >>> @@ -295,12 +305,13 @@
> >>>     if (verbose)
> >>>     {
> >>>         cout << rdata.is_interaction_excluded
> >>> -                << " <-irdata.is_interaction_excluded\n";
> >>> +             << " <-rdata.is_interaction_excluded\n";
> >>>         // std::cout << "invvarmatrix:\n";
> >>>         // invvarmatrixin.masked_data->print();
> >>>         std::cout << "rdata.X:\n";
> >>>         rdata.X.print();
> >>>     }
> >>> +
> >>>     mematrix<double> X = apply_model(rdata.X, model, interaction,
> ngpreds,
> >>>                                      rdata.is_interaction_excluded,
> false,
> >>>                                      nullmodel);
> >>> @@ -311,6 +322,7 @@
> >>>         std::cout << "Y:\n";
> >>>         rdata.Y.print();
> >>>     }
> >>> +
> >>>     int length_beta = X.ncol;
> >>>     beta.reinit(length_beta, 1);
> >>>     sebeta.reinit(length_beta, 1);
> >>>
> >>> Modified: pkg/ProbABEL/src/regdata.cpp
> >>> ===================================================================
> >>> --- pkg/ProbABEL/src/regdata.cpp    2013-08-08 10:07:32 UTC (rev 1285)
> >>> +++ pkg/ProbABEL/src/regdata.cpp    2013-08-08 11:19:30 UTC (rev 1286)
> >>> @@ -39,7 +39,7 @@
> >>>
> >>>     for (int i = 0; i < nids; i++)
> >>>     {
> >>> -        masked_data[i] = 0;
> >>> +        masked_data[i] = obj.masked_data[i];
> >>>     }
> >>> }
> >>>
> >>> @@ -95,6 +95,9 @@
> >>>
> >>> void regdata::update_snp(gendata &gend, int snpnum)
> >>> {
> >>> +    // Add genotypic data (dosage or probabilities) to the design
> >>> +    // matrix X.
> >>> +
> >>>     for (int j = 0; j < ngpreds; j++)
> >>>     {
> >>>         double snpdata[nids];
> >>> @@ -109,11 +112,34 @@
> >>>         {
> >>>             X.put(snpdata[i], i, (ncov - j));
> >>>             if (isnan(snpdata[i]))
> >>> +            {
> >>>                 masked_data[i] = 1;
> >>> +            }
> >>>         }
> >>>     }
> >>> }
> >>>
> >>> +void regdata::remove_snp_from_X()
> >>> +{
> >>> +    // update_snp() adds SNP information to the design matrix. This
> >>> +    // function allows you to strip that information from X again.
> >>> +    // This is used for example when calculating the null model.
> >>> +
> >>> +    if(ngpreds == 1)
> >>> +    {
> >>> +        X.delete_column(X.ncol -1);
> >>> +    }
> >>> +    else if(ngpreds == 2)
> >>> +    {
> >>> +        X.delete_column(X.ncol -1);
> >>> +        X.delete_column(X.ncol -1);
> >>> +    }
> >>> +    else
> >>> +    {
> >>> +        cerr << "ngpreds should be 1 or 2. you should never come
> here!\n";
> >>> +    }
> >>> +}
> >>> +
> >>> regdata::~regdata()
> >>> {
> >>>     delete[] regdata::masked_data;
> >>>
> >>> Modified: pkg/ProbABEL/src/regdata.h
> >>> ===================================================================
> >>> --- pkg/ProbABEL/src/regdata.h    2013-08-08 10:07:32 UTC (rev 1285)
> >>> +++ pkg/ProbABEL/src/regdata.h    2013-08-08 11:19:30 UTC (rev 1286)
> >>> @@ -34,6 +34,7 @@
> >>>             bool ext_is_interaction_excluded);
> >>>     mematrix<double> extract_genotypes();
> >>>     void update_snp(gendata &gend, int snpnum);
> >>> +    void remove_snp_from_X();
> >>>     regdata get_unmasked_data();
> >>>     ~regdata();
> >>>
> >>>
> >>> _______________________________________________
> >>> Genabel-commits mailing list
> >>> Genabel-commits at lists.r-forge.r-project.org
> >>>
> https://lists.r-forge.r-project.org/cgi-bin/mailman/listinfo/genabel-commits
> >> _______________________________________________
> >> genabel-devel mailing list
> >> genabel-devel at lists.r-forge.r-project.org
> >>
> https://lists.r-forge.r-project.org/cgi-bin/mailman/listinfo/genabel-devel
> >>
> >
> >
> >
> >
> > _______________________________________________
> > genabel-devel mailing list
> > genabel-devel at lists.r-forge.r-project.org
> >
> https://lists.r-forge.r-project.org/cgi-bin/mailman/listinfo/genabel-devel
> >
>
> --
> -----------------------------------------------------------------
> L.C. Karssen
> Utrecht
> The Netherlands
>
> lennart at karssen.org
> http://blog.karssen.org
>
> Stuur mij aub geen Word of Powerpoint bestanden!
> Zie http://www.gnu.org/philosophy/no-word-attachments.nl.html
> ------------------------------------------------------------------
>
>
> _______________________________________________
> genabel-devel mailing list
> genabel-devel at lists.r-forge.r-project.org
> https://lists.r-forge.r-project.org/cgi-bin/mailman/listinfo/genabel-devel
>



-- 
-----------------------------------------------------
Yurii S. Aulchenko

[ LinkedIn <http://nl.linkedin.com/in/yuriiaulchenko> ] [
Twitter<http://twitter.com/YuriiAulchenko>] [
Blog <http://yurii-aulchenko.blogspot.nl/> ]
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