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GEMMA GSL ERROR: function value is not finite in brent.c

In github issue 210 this comes up. @hrwang was kind enough to send me a dataset that brings up this error. Now we stand a chance of doing something about it! As in

napoli:~/iwrk/opensource/code/genetics/gemma/tmp/issue210$ ../../bin/gemma -bfile 20 -k BS_kinship.sXX.txt -lmm 1 -c Covariate_PC3.txt -n 1 -o outname
GEMMA 0.99.0-pre1 (2021-08-11) by Xiang Zhou, Pjotr Prins and team (C) 2012-2021
Reading Files ...
## number of total individuals = 727
## number of analyzed individuals = 57
## number of covariates = 4
## number of phenotypes = 1
## number of total SNPs/var        =   215451
## number of analyzed SNPs         =    72731
Start Eigen-Decomposition...
pve estimate =0.956403
se(pve) =0.255427
GSL ERROR: function value is not finite in newton.c at line 88 errno 9

Next I ran with the debug switch and it stops with the slightly more informative

../../bin/gemma -bfile 20 -k BS_kinship.sXX.txt -lmm 1 -c Covariate_PC3.txt -n 1 -o outname -debug
GEMMA 0.99.0-pre1 (2021-08-11) by Xiang Zhou, Pjotr Prins and team (C) 2012-2021
GSL random generator type: mt19937; seed = 25479 (option -1); first value = 191757793
Reading Files ...
## number of total individuals = 727
## number of analyzed individuals = 57
## number of covariates = 4
## number of phenotypes = 1
## number of total SNPs/var        =   215451
## number of analyzed SNPs         =    72731
Start Eigen-Decomposition...
pve estimate =0.956403
se(pve) =0.255427
ERROR: Enforce failed for Trying to take the log of 0.000000 in src/mathfunc.cpp at line 118 in safe_log

Next step is rebuilding gemma with debug info `make debug` and rerun in the debugger. A backtrace of

gdb --args ../../bin/gemma -bfile 20 -k BS_kinship.sXX.txt -lmm 1 -c Covariate_PC3.txt -n 1 -o outname -debug

shows

#2  0x000000000047dcb0 in safe_log (d=d@entry=0) at src/mathfunc.cpp:118
#3  0x00000000004707ea in LogRL_f (l=l@entry=1.0000000000000001e-05, params=params@entry=0x7fffffffcc20)
    at src/lmm.cpp:851
#4  0x0000000000471b05 in CalcLambda (func_name=func_name@entry=82 'R', params=...,
    l_min=l_min@entry=1.0000000000000001e-05, l_max=100000, n_region=10,
    lambda=@0x7fffffffccc8: 3.2054654756518093, logf=@0x7fffffffcca0: 0.83040722111380116)
    at src/lmm.cpp:1970
#5  0x0000000000475cac in LMM::AnalyzePlink (this=this@entry=0x7fffffffd1a0, U=U@entry=0x4fcc80,
    eval=eval@entry=0x52dff0, UtW=UtW@entry=0x4fccc0, Uty=Uty@entry=0x7fffffffd140, W=W@entry=0x4fe140,
    y=<optimized out>, gwasnps=...) at src/lmm.cpp:1860
#6  0x00000000004359f5 in GEMMA::BatchRun (this=this@entry=0x7fffffffe720, cPar=...)
    at src/gemma.cpp:2798
#7  0x000000000047bed0 in main (argc=14, argv=0x7fffffffe888) at src/main.cpp:86

In this case a SNP for some reason balks. Another run, after disabling the log check renders

#0  0x00007ffff5e1deca in raise ()
   from /gnu/store/fa6wj5bxkj5ll1d7292a70knmyl7a0cr-glibc-2.31/lib/libpthread.so.0
#1  0x00000000004245ba in gemma_gsl_error_handler (reason=<optimized out>, file=<optimized out>,
    line=88, gsl_errno=<optimized out>) at src/gemma.cpp:75
#2  0x00007ffff7e59f6d in newton_iterate ()
   from /gnu/store/qsr7pw4cbka4qhxm3h0bkwwl7h08qfmw-profile/lib/libgsl.so.25
#3  0x0000000000471cba in CalcLambda (func_name=func_name@entry=82 'R', params=...,
    l_min=l_min@entry=1.0000000000000001e-05, l_max=100000, n_region=<optimized out>,
    lambda=@0x7fffffffccc8: 1.0000000000000001e-05, logf=@0x7fffffffcca0: 507.88508012472289)
    at src/lmm.cpp:2040

points out that in line 2040 `gsl_root_fdfsolver_iterate` is not happy executing a Newton root solver. What is interesting is that, in this case, the gemma_gsl_error_handler is called and stops processing. We now have three ways to stop GEMMA from the same error!

The original version bails out inside GSL:

GSL ERROR: function value is not finite in newton.c at line 88 errno 9

#0  0x00007ffff5e1deca in raise ()
   from /gnu/store/fa6wj5bxkj5ll1d7292a70knmyl7a0cr-glibc-2.31/lib/libpthread.so.0
#1  0x00007ffff7e59f6d in newton_iterate ()
   from /gnu/store/qsr7pw4cbka4qhxm3h0bkwwl7h08qfmw-profile/lib/libgsl.so.25
#2  0x000000000047a9c5 in CalcLambda(char, FUNC_PARAM&, double, double, unsigned long, double&, double&) [clone .constprop.671] ()

@hrwang had a good suggestion to make sure that the output for the SNP is made invalid and to continue processing. Disabling the error handler let GEMMA continue. I added a check for the status flag to make sure output was set to invalid (nan). In the test set 178 out of 72732 SNPs failed.


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