linearization

Author

Saideep Gona

Published

November 16, 2023

Context

Now that I have a working model of gene expression prediction in flu from Enformer predictions, I can continue with the linearization process.

1.) Convert gene centered GEUVADIS predictions to single values

Charles has already generated geuvadis predictions at gene TSS sites stored as 4x5313 per gene and individual combo. I need these to be averaged into 1x5313 and in a format which can be easily read to be predicted by my glmnet. The code below accomplishes this.

Code
import os,sys

import h5py
import numpy as np


with open("/beagle3/haky/users/saideep/github_repos/Daily-Blog-Sai/posts/2023-11-16-linearization/individuals.txt", "r") as inds_f:
    inds = inds_f.read().split()

# gene_list = []
# c=0
# with open("/beagle3/haky/users/charles/project/singleXcanDL/PredicDB/LCL_PredictDb/files/Gene_anno.txt", "r") as genes_f:
#     for line in genes_f:
#         if c==0:
#             c+=1
#             continue
#         gene_list.append("chr"+"_".join([line.split("\t")[x] for x in [0,3,4]]))

# print(gene_list)

enformer_geuvadis_pred_folder = "/beagle3/haky/data/Geuvadis_TSS_enformer_prediction"

with h5py.File(os.path.join(enformer_geuvadis_pred_folder, inds[0]+".h5"), "r") as f:
    genes_dsets = list(f.keys())
    genes_dsets.sort()
Code

# dset_lengths = []
# c=0
# for ind in inds:
#     if os.path.exists(os.path.join(enformer_geuvadis_pred_folder, ind+".h5")):
#         with h5py.File(os.path.join(enformer_geuvadis_pred_folder, ind+".h5"), "r") as f:
#             dset_lengths.append(len(f.keys()))
#             print(c)
#             c+=1
#     else:
#         print(ind)

# print(dset_lengths)



for ind in inds:
    if os.path.exists(os.path.join("/beagle3/haky/users/saideep/projects/aracena_modeling/linearization",ind+".txt")):
        continue
    expression_array = np.zeros((len(genes_dsets),5313))
    if os.path.exists(os.path.join(enformer_geuvadis_pred_folder, ind+".h5")):
        with h5py.File(os.path.join(enformer_geuvadis_pred_folder, ind+".h5"), "r") as f:
            for i, gene in enumerate(genes_dsets):
                # print(i)
                # print(np.mean(f[gene][:,:],axis=0).shape)
                expression_array[i,:] = np.mean(f[gene][:,:],axis=0)
            np.savetxt(os.path.join("/beagle3/haky/users/saideep/projects/aracena_modeling/linearization",ind+".txt"),expression_array)
    else:
        print(ind)


HG00107
HG00113
HG00128
HG00140
HG00190
Code

with h5py.File(os.path.join(enformer_geuvadis_pred_folder, inds[63]+".h5"), "r") as f:
    print(len(f.keys()))
19563

3.) Collect predictions into expression table

After the above steps, predict_for_linearization.qmd was run in order to generate predictions from all the GEUVADIS inputs. These predictions need to be combined and formatted for use in the predixcan pipeline in order to perform the linearization.

This will be done here. First lets join the individual columns together

Code
import os,sys
import h5py

with open("/beagle3/haky/users/saideep/github_repos/Daily-Blog-Sai/posts/2023-11-16-linearization/individuals.txt", "r") as inds_f:
    inds = inds_f.read().split()

enformer_geuvadis_pred_folder = "/beagle3/haky/data/Geuvadis_TSS_enformer_prediction"

with h5py.File(os.path.join(enformer_geuvadis_pred_folder, inds[0]+".h5"), "r") as f:
    genes_dsets = list(f.keys())
    genes_dsets.sort()


paste_com = [
    "paste",
    "-d'\t'"
]

inds_include = []
for ind in inds:
    if os.path.exists(os.path.join("/beagle3/haky/users/saideep/projects/aracena_modeling/linearization",ind+"_preds.txt")):
        paste_com.append(os.path.join("/beagle3/haky/users/saideep/projects/aracena_modeling/linearization",ind+"_preds.txt"))
        inds_include.append(ind)

paste_com.append("|")
paste_com.append("tail")
paste_com.append("-n")
paste_com.append("+2")

paste_com.append(">")
paste_com.append(os.path.join("/beagle3/haky/users/saideep/projects/aracena_modeling/linearization","combined_expression.txt"))

print(" ".join(paste_com))

os.system(" ".join(paste_com))
paste -d'   ' /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00096_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00097_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00099_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00100_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00101_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00102_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00103_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00104_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00105_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00106_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00108_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00109_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00110_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00111_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00112_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00114_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00115_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00116_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00117_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00118_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00119_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/HG00120_preds.txt 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/beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20586_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20588_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20589_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20752_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20754_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20756_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20757_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20758_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20759_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20760_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20761_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20765_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20766_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20768_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20769_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20770_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20771_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20772_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20773_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20774_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20778_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20783_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20785_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20786_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20787_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20790_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20792_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20795_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20796_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20797_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20798_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20799_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20800_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20801_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20802_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20803_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20804_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20805_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20806_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20807_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20808_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20809_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20810_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20811_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20812_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20813_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20814_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20815_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20816_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20819_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20826_preds.txt /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/NA20828_preds.txt | tail -n +2 > /beagle3/haky/users/saideep/projects/aracena_modeling/linearization/combined_expression.txt
0
Code
import pandas as pd


combined_expression_table = pd.read_csv(os.path.join("/beagle3/haky/users/saideep/projects/aracena_modeling/linearization","combined_expression.txt"), delimiter="\t", header=None)

combined_expression_table.columns = inds_include
Code
# Create mapping of gene regions to ensemble gene ids
gene_region_mapping = {}
c=0
with open("/beagle3/haky/users/saideep/github_repos/Daily-Blog-Sai/posts/2023-11-16-linearization/canonical_TSS_full_metadata.txt", "r") as genes_f:
    for line in genes_f:
        if c==0:
            c+=1
            continue
        tss_region = line.strip().split(",")[9].split("_")
        tss_plus_one = "_".join([tss_region[0],str(int(tss_region[1])-1),str(int(tss_region[2])-1)])
        gene_region_mapping[tss_plus_one] = line.split(",")[0]

# Filter gene list for genes not in the gene annotation file
include_gene = []
gene_ids = []
for gene in genes_dsets:
    cur_gene_region = gene.rstrip("_predictions")
    if cur_gene_region not in gene_region_mapping:
        print(cur_gene_region)
        include_gene.append(False)
    else:
        gene_ids.append(gene_region_mapping[cur_gene_region])
        include_gene.append(True)

combined_expression_table_genes_in_anno = combined_expression_table[include_gene]
combined_expression_table_genes_in_anno.index = gene_ids
Code
combined_expression_table_genes_in_anno.to_csv(os.path.join("/beagle3/haky/users/saideep/projects/aracena_modeling/linearization","combined_expression_labeled.csv"), index=True, index_label="NAME")
combined_expression_table_genes_in_anno
HG00096 HG00097 HG00099 HG00100 HG00101 HG00102 HG00103 HG00104 HG00105 HG00106 ... NA20810 NA20811 NA20812 NA20813 NA20814 NA20815 NA20816 NA20819 NA20826 NA20828
ENSG00000107554 -0.067708 -0.069715 -0.067695 -0.065804 -0.066442 -0.070470 -0.069931 -0.066396 -0.069017 -0.068121 ... -0.066092 -0.079097 -0.072408 -0.072700 -0.068084 -0.079158 -0.065807 -0.073517 -0.068969 -0.067933
ENSG00000120054 -0.043449 -0.044064 -0.044349 -0.042859 -0.043716 -0.043965 -0.044212 -0.044322 -0.044301 -0.044090 ... -0.043625 -0.042630 -0.044360 -0.044357 -0.043995 -0.043175 -0.043779 -0.043147 -0.043031 -0.043770
ENSG00000107566 0.246413 0.247575 0.254017 0.244225 0.245029 0.246469 0.253154 0.258049 0.249720 0.255736 ... 0.245446 0.244844 0.252450 0.246691 0.254097 0.266294 0.244424 0.247727 0.247761 0.244369
ENSG00000213341 0.078040 0.077490 0.084288 0.076513 0.077776 0.078267 0.079760 0.086668 0.079473 0.085564 ... 0.077617 0.078623 0.082075 0.077816 0.083754 0.082068 0.076547 0.078124 0.077698 0.077902
ENSG00000095485 0.224175 0.216422 0.219703 0.218413 0.224677 0.226130 0.217048 0.218370 0.215557 0.225863 ... 0.231997 0.216629 0.218340 0.217358 0.217651 0.217105 0.218990 0.225677 0.218895 0.217907
... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ...
ENSG00000147202 0.616342 0.616342 0.616342 0.616342 0.616342 0.616342 0.616342 0.616342 0.616342 0.616342 ... 0.616342 0.616342 0.616342 0.616342 0.616342 0.616342 0.616342 0.616342 0.616342 0.616342
ENSG00000204086 0.087435 0.087435 0.087435 0.087435 0.087435 0.087435 0.087435 0.087435 0.087435 0.087435 ... 0.087435 0.087435 0.087435 0.087435 0.087435 0.087435 0.087435 0.087435 0.087435 0.087435
ENSG00000101850 0.008612 0.008612 0.008612 0.008612 0.008612 0.008612 0.008612 0.008612 0.008612 0.008612 ... 0.008612 0.008612 0.008612 0.008612 0.008612 0.008612 0.008612 0.008612 0.008612 0.008612
ENSG00000146950 -0.002481 -0.002481 -0.002481 -0.002481 -0.002481 -0.002481 -0.002481 -0.002481 -0.002481 -0.002481 ... -0.002481 -0.002481 -0.002481 -0.002481 -0.002481 -0.002481 -0.002481 -0.002481 -0.002481 -0.002481
ENSG00000234469 0.111147 0.111147 0.111147 0.111147 0.111147 0.111147 0.111147 0.111147 0.111147 0.111147 ... 0.111147 0.111147 0.111147 0.111147 0.111147 0.111147 0.111147 0.111147 0.111147 0.111147

19563 rows × 448 columns

Code
genes_dsets
['chr10_100009946_100009948_predictions',
 'chr10_100081868_100081870_predictions',
 'chr10_100186028_100186030_predictions',
 'chr10_100229595_100229597_predictions',
 'chr10_100267637_100267639_predictions',
 'chr10_100286679_100286681_predictions',
 'chr10_100330227_100330229_predictions',
 'chr10_100347232_100347234_predictions',
 'chr10_100463008_100463010_predictions',
 'chr10_100519860_100519862_predictions',
 'chr10_100529870_100529872_predictions',
 'chr10_100535942_100535944_predictions',
 'chr10_100745581_100745583_predictions',
 'chr10_100912962_100912964_predictions',
 'chr10_100969503_100969505_predictions',
 'chr10_100987496_100987498_predictions',
 'chr10_100987542_100987544_predictions',
 'chr10_100999807_100999809_predictions',
 'chr10_101031128_101031130_predictions',
 'chr10_101031233_101031235_predictions',
 'chr10_101061988_101061990_predictions',
 'chr10_101131299_101131301_predictions',
 'chr10_101229462_101229464_predictions',
 'chr10_101354164_101354166_predictions',
 'chr10_101588256_101588258_predictions',
 'chr10_101588320_101588322_predictions',
 'chr10_101695169_101695171_predictions',
 'chr10_101776113_101776115_predictions',
 'chr10_101783445_101783447_predictions',
 'chr10_101818443_101818445_predictions',
 'chr10_101843799_101843801_predictions',
 'chr10_102056172_102056174_predictions',
 'chr10_102065348_102065350_predictions',
 'chr10_102120367_102120369_predictions',
 'chr10_102133039_102133041_predictions',
 'chr10_102152388_102152390_predictions',
 'chr10_102226298_102226300_predictions',
 'chr10_102241511_102241513_predictions',
 'chr10_102245531_102245533_predictions',
 'chr10_102395704_102395706_predictions',
 'chr10_102418784_102418786_predictions',
 'chr10_102420835_102420837_predictions',
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 'chr10_102461394_102461396_predictions',
 'chr10_102502711_102502713_predictions',
 'chr10_102503971_102503973_predictions',
 'chr10_1025858_1025860_predictions',
 'chr10_102644478_102644480_predictions',
 'chr10_102714396_102714398_predictions',
 'chr10_102714635_102714637_predictions',
 'chr10_102743947_102743949_predictions',
 'chr10_102837412_102837414_predictions',
 'chr10_102854258_102854260_predictions',
 'chr10_102869469_102869471_predictions',
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 'chr10_103193271_103193273_predictions',
 'chr10_103245886_103245888_predictions',
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 'chr10_103351139_103351141_predictions',
 'chr10_103367975_103367977_predictions',
 'chr10_103396474_103396476_predictions',
 'chr10_103396625_103396627_predictions',
 'chr10_103452369_103452371_predictions',
 'chr10_103458899_103458901_predictions',
 'chr10_103479239_103479241_predictions',
 'chr10_103493704_103493706_predictions',
 'chr10_103855575_103855577_predictions',
 'chr10_103918183_103918185_predictions',
 'chr10_103967139_103967141_predictions',
 'chr10_104085879_104085881_predictions',
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 'chr10_104232363_104232365_predictions',
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 'chr10_104269183_104269185_predictions',
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 'chr10_104641289_104641291_predictions',
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 'chr10_107164705_107164707_predictions',
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 'chr10_110644335_110644337_predictions',
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 'chr10_110919603_110919605_predictions',
 'chr10_111077028_111077030_predictions',
 'chr10_112183764_112183766_predictions',
 'chr10_112283399_112283401_predictions',
 'chr10_112374115_112374117_predictions',
 'chr10_112446913_112446915_predictions',
 'chr10_112447214_112447216_predictions',
 'chr10_112950246_112950248_predictions',
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 'chr10_113854081_113854083_predictions',
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 'chr10_114174202_114174204_predictions',
 'chr10_114179352_114179354_predictions',
 'chr10_114239253_114239255_predictions',
 'chr10_114404501_114404503_predictions',
 'chr10_114658274_114658276_predictions',
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 'chr10_119029713_119029715_predictions',
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 'chr10_12042808_12042810_predictions',
 'chr10_120457226_120457228_predictions',
 'chr10_12068953_12068955_predictions',
 'chr10_120851361_120851363_predictions',
 'chr10_12129676_12129678_predictions',
 'chr10_121598443_121598445_predictions',
 'chr10_121928030_121928032_predictions',
 'chr10_12195890_12195892_predictions',
 'chr10_12196187_12196189_predictions',
 'chr10_121975216_121975218_predictions',
 'chr10_121989162_121989164_predictions',
 'chr10_122271295_122271297_predictions',
 'chr10_122374707_122374709_predictions',
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 'chr10_122461552_122461554_predictions',
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 'chr10_122699845_122699847_predictions',
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 'chr10_122879580_122879582_predictions',
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 'chr10_123008794_123008796_predictions',
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 'chr10_123666354_123666356_predictions',
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 'chr10_125719708_125719710_predictions',
 'chr10_125775820_125775822_predictions',
 'chr10_125823257_125823259_predictions',
 'chr10_125823545_125823547_predictions',
 'chr10_125881291_125881293_predictions',
 'chr10_125896563_125896565_predictions',
 'chr10_126388476_126388478_predictions',
 'chr10_126670692_126670694_predictions',
 'chr10_126905427_126905429_predictions',
 'chr10_127196590_127196592_predictions',
 'chr10_127549308_127549310_predictions',
 'chr10_127737184_127737186_predictions',
 'chr10_127892940_127892942_predictions',
 'chr10_127907102_127907104_predictions',
 'chr10_128126422_128126424_predictions',
 'chr10_129467240_129467242_predictions',
 'chr10_129964273_129964275_predictions',
 'chr10_13001712_13001714_predictions',
 'chr10_130110829_130110831_predictions',
 'chr10_130136390_130136392_predictions',
 'chr10_13100162_13100164_predictions',
 'chr10_131311720_131311722_predictions',
 'chr10_13161557_13161559_predictions',
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