Hi,

I'm trying to use your fantastic software fastENLOC version 2, but to my regret the compiled binary file doesn't work well in my environment.
I encountered a similar thread (#3) and found that static linked version of compiled Linux executable "fastenloc.static" you have added worked well.

To my understanding this is a binary file for fastENLOC (version 1), so would you add the similar static version of compiled Linux executable in fastENLOC version 2?
Thank you in advance.

Taka

Hi,

I'm having a strange issue where a variant is not being used in the analysis, as it is not in the SNP based output.
The variant is in both GTEx and my GWAS. Furthermore, I'm getting results for the SNP in some tissues, but not all (in my case, thyroid is my tissue of interest). In this case, I used the pre-computed GTEx file that you provide.

I checked, and the variant in question (chr11_68450822_C_T_b38) seems to be an eQTL in thyroid, and has a MAF of ~0.24.
Any ideas why its not being used for thyroid (and some other tissues)?

Thanks

Do you have a script you can share for assigning LD blocks from LDetect to a GWAS output file such as below?

chr1_13550_G_A_b38 Loc1

Thank you

Hi,

This could be a stupid question.

I have used fastenloc to perform colocalization of fine-mapped GWAS and fine-mapped GTExv8 data (all tissues). I read this in enloc paper:
"we propose computing a regional colocalization probability, or RCP, by summing up the SNP-level colocalization probabilities :(SCPs) of correlated SNPs within an LD block that harbors a single GWAS association signal."

But when I sum up the SCP (in SNP-level colocalization result file) of one specific signal in one specific tissue, it is smaller than the RCP I see in the Signal-level colocalization result file. Is my understanding of RCP and SCP wrong?

Many thanks in advance.

Hi there,

I am trying to install the fastENLOC in HPC environment with Linux OS. Here is the error message that I encountered.

g++ -c  main.cc
g++ -fopenmp   -c  controller.cc
In file included from /appl/boost-1.60.0/include/boost/iostreams/detail/is_dereferenceable.hpp:12,
                 from /appl/boost-1.60.0/include/boost/iostreams/detail/resolve.hpp:26,
                 from /appl/boost-1.60.0/include/boost/iostreams/detail/push.hpp:24,
                 from /appl/boost-1.60.0/include/boost/iostreams/chain.hpp:29,
                 from /appl/boost-1.60.0/include/boost/iostreams/copy.hpp:28,
                 from controller.cc:7:
/appl/boost-1.60.0/include/boost/type_traits/detail/bool_trait_def.hpp:18:79: note: #pragma message: NOTE: Use of this header (bool_trait_def.hpp) is deprecated
 # pragma message("NOTE: Use of this header (bool_trait_def.hpp) is deprecated")
                                                                               ^
In file included from /appl/boost-1.60.0/include/boost/type_traits/detail/bool_trait_def.hpp:21,
                 from /appl/boost-1.60.0/include/boost/iostreams/detail/is_dereferenceable.hpp:12,
                 from /appl/boost-1.60.0/include/boost/iostreams/detail/resolve.hpp:26,
                 from /appl/boost-1.60.0/include/boost/iostreams/detail/push.hpp:24,
                 from /appl/boost-1.60.0/include/boost/iostreams/chain.hpp:29,
                 from /appl/boost-1.60.0/include/boost/iostreams/copy.hpp:28,
                 from controller.cc:7:
/appl/boost-1.60.0/include/boost/type_traits/detail/template_arity_spec.hpp:13:84: note: #pragma message: NOTE: Use of this header (template_arity_spec.hpp) is deprecated
 # pragma message("NOTE: Use of this header (template_arity_spec.hpp) is deprecated")
                                                                                    ^
In file included from /appl/boost-1.60.0/include/boost/iostreams/detail/is_dereferenceable.hpp:13,
                 from /appl/boost-1.60.0/include/boost/iostreams/detail/resolve.hpp:26,
                 from /appl/boost-1.60.0/include/boost/iostreams/detail/push.hpp:24,
                 from /appl/boost-1.60.0/include/boost/iostreams/chain.hpp:29,
                 from /appl/boost-1.60.0/include/boost/iostreams/copy.hpp:28,
                 from controller.cc:7:
/appl/boost-1.60.0/include/boost/type_traits/detail/template_arity_spec.hpp:13:84: note: #pragma message: NOTE: Use of this header (template_arity_spec.hpp) is deprecated
 # pragma message("NOTE: Use of this header (template_arity_spec.hpp) is deprecated")
                                                                                    ^
In file included from /appl/boost-1.60.0/include/boost/iostreams/copy.hpp:28,
                 from controller.cc:7:
/appl/boost-1.60.0/include/boost/iostreams/chain.hpp: In member function ‘void boost::iostreams::detail::chain_base<Self, Ch, Tr, Alloc, Mode>::push_impl(const T&, std::streamsize, std::streamsize)’:
/appl/boost-1.60.0/include/boost/iostreams/chain.hpp:256:14: warning: ‘template<class> class std::auto_ptr’ is deprecated [-Wdeprecated-declarations]
         std::auto_ptr<streambuf_t>
              ^~~~~~~~
In file included from /misc/appl/gcc-8.2.0/include/c++/8.2.0/memory:80,
                 from /appl/boost-1.60.0/include/boost/config/no_tr1/memory.hpp:21,
                 from /appl/boost-1.60.0/include/boost/get_pointer.hpp:14,
                 from /appl/boost-1.60.0/include/boost/bind/mem_fn.hpp:25,
                 from /appl/boost-1.60.0/include/boost/mem_fn.hpp:22,
                 from /appl/boost-1.60.0/include/boost/bind/bind.hpp:26,
                 from /appl/boost-1.60.0/include/boost/bind.hpp:22,
                 from /appl/boost-1.60.0/include/boost/iostreams/copy.hpp:26,
                 from controller.cc:7:
/misc/appl/gcc-8.2.0/include/c++/8.2.0/bits/unique_ptr.h:53:28: note: declared here
   template<typename> class auto_ptr;
                            ^~~~~~~~
g++ -c sigCluster.cc 
g++ -fopenmp -O3 main.o controller.o sigCluster.o  -lm -lgsl -lgslcblas -lboost_iostreams -lz  -o fastenloc
/usr/bin/ld: cannot find -lgsl
/usr/bin/ld: cannot find -lgslcblas
/usr/bin/ld: cannot find -lboost_iostreams
collect2: error: ld returned 1 exit status
make: *** [main] Error 1

What should I do?

Dear William,

I noticed hat if the provided input is compressed using bgzip (rather than gzip), fastENLOC will read all of its contents except the last line without reporting any error. Is this expected behavior?

As stated in the bgzip manual, bgzip is compatible with gzip, however going through fastenloc code I figured that the library used to decompress files is boost::iostreams::gzip_decompressor(), and in htslib github I found this issue which may be related to the issue I am experiencing with fastENLOC. Since bgzip is at least in my experience very often used especially with vcf files, it could be useful mentioning this in fastenloc documentation.

I am looking forward to hearing your thoughts on this. Thanks in advance!

Best,

probalica19

Hi !
Prof. @xqwen

I am preparing GWAS PIP input using torus .
When I run the example code "torus -d Height.torus.zval.gz --load_zval -dump_pip Height.gwas.pip" ,
I noticed there are 4 columns in the output file "Height.gwas.pip" .
I think the fourth column is the prior probability for a SNP to be causal, but how is this value determined?

Thank you so much for your reply

Dear William,
How to get the casual gene or SNP by using the fast enloc?
Yours sincerely,
Altaman

For the -total_variants flag, what are the total variants?

If I am using GTEx data and some GWAS, are the total variants the max number of variants in the two datasets? Or is it the number of variants genotyped by GTEx (~46 million)? For example, the VCF files you provide doesn't have all variants genotyped by GTEx. So would it be the number of SNPs in the VCF or the total number of genotyped GTEx variants?

Hi,
I'm using fastenloc to integrate an eQTL data and a GWAS data, however they are from different population (Asian eQTL and european GWAS).
I wonder if fastenloc can handle this situation? Or there are some ways to add two populations' LD information to the procedure?

Jiang

Do you think there is a chance to get the sQTL vcf file for GTEx V8?

Hi,

I am running fastENLOC on a large scale and I am noticing that for some samples when there are no overlaps between GWAS loci and eQTL loci, the tool doesn't fail but keeps on running, which makes it really hard to debug.

Here is an example:

Computing colocalization probabilities ...

Processing eQTL annotations ...
read in 288 SNPs, 16 eQTL signal clusters, 2.1 expected eQTLs

Processing complex trait data ...
read in 288 SNPs (eQTL+gwas), 0 GWAS loci, 0.0 expected hits

and the tool goes on forever. I noticed the same behavior when there are no eQTL loci.

Can this be fixed, or can you recommend a way of handing this?

Just as a note, I am working with predefined regions, so in order to save space I am using GTEx eQTL annotation files that I have previously subsetted to a region of interest using tabix.

Thank you in advance!

probalica

Hello,
Which data were used to generate the pre-computed GTEx multi-tissue eQTL annotation VCFs that you provide?
Was it only the significant GTEx eQTLs, or all SNP-gene associations?

I'm trying to run my data after completing all previous steps. However, I keep getting the following line when running fastenloc -eqtl gtex_v8.eqtl_annot.vcf.gz -gwas morris.pip.gz -total_variants 17000000 -t Thyroid

Processing complex trait data ...
read in 13921173 SNPs (eQTL+gwas), 22 GWAS loci, 22.0 expected hits

As you can see, only 22 loci are considered. However, I have ~1700 loci, which I added using format2torus.pl
Do you have any idea what might be causing this?
Thanks

Hi,

I have noticed that these two commands yield slightly different results.

fastenloc -g sim_data/gwas.pip.gz -e sim_data/eqtl.vcf.gz -prefix fastenloc_out/sim -tv 30000000 --all

and

fastenloc -g sim_data/gwas.pip.gz -e sim_data/eqtl.vcf.gz -prefix fastenloc_out/sim -tv 30000000 --all -thread 8

This commands and input files are from fastenloc/promise_and_limitation_paper/empirical_power_evaluation directory. When I compare my results to the ones in fasteloc_output folder in the same location, only the files produced by the first of the above mentioned commands yields the same results.

Is this behavior expected?

Thanks!

probalica19

Does the direction of effect of a SNP in a GWAS affect colocalization? That is to say, does it matter if the provided z-score is positive or negative?

Thanks

Hi Xiaoquan, I'm interested in using fastENLOC on a two GWAS's (Diabetes and BMI). Would you recommend using fastENLOC on two non-eQTL/molecular QTL datasets? Would there be differences in modelling such that I should use a different program?

Dear Xiaoquan,

I want to confirm that Open Targets applied FastenLoc as the underlying Colocalization Analysis, Correct?

Thanks.

Shicheng

Hi,

I am wondering whether fastENLOC gives different results from enloc?
Since I am trying to run enloc now, I am not sure if I should switch to fastENLOC.
If fastENLOC reports different region colocalization probability from enloc, then I will definitely switch to it.

Thanks so much!

Hello,
is the "Multi-tissue eQTL annotation with hg38 position ID" file based on significant cis-eQTL or ALL cis-eQTL associations?

Furthermore, where can I find a VCF file with all GTEx V8 annotations, in case I want to derive my own annotations?

Thanks

Hello,
What ensembl version are the ensembl IDs drawn from in the GTEx annotation files?

Thanks

Can fastenloc be run by chromosome?

fastenloc output includes multiple results for each gene, in the format of
ENSG00000xxxx:1
ENSG00000xxxx:2

Can you please explain the difference between these?
Thanks

Hi,

Is there a resource on guidance for choosing an appropriate shrinkage value? Should it be calibrated based on the expected hit number or the *enloc.enrich.out values?

Thanks