Preprocess

Functions to preprocess sequence to prepare kinase substrate dataset

Setup

from katlas.utils import *

Data processing

source

get_diff

 get_diff (df1, df2, col1, col2=None)

Get non-overlap parts of two dataframes.

df1 = pd.DataFrame({'gene': ['A', 'B', 'C']})
df2 = pd.DataFrame({'gene': ['B', 'C', 'D']})

df1_unq, df2_unq = get_diff(df1, df2, 'gene')
df1_unq
gene
0 A 
df2_unq
gene
2 D

Checker

In many phosphorylation datsets, there are amino acids in the site sequence that are in lower case but does not belong to s/t/y. Also, there are uncommon amino acids such as U or O that appear in the sequence. Therefore, it is essential to convert the sequence string for kinase ranking.

source

check_seq

 check_seq (seq)

Convert non-s/t/y characters to uppercase and replace disallowed characters with underscores.

try:
    check_seq('aaadaaa')
except Exception as e:
    print(e)
aaadaaa has d at position 3; need to have one of 's', 't', or 'y' in the center
check_seq('AAkUuPSFstTH') # if the center amino acid does not belong to sty/STY, will raise an error
'AAK__PSFstTH'

source

check_seq_df

 check_seq_df (df, col)

Convert non-s/t/y to upper case & replace with underscore if the character is not in the allowed set

df=Data.get_human_site()
df.head()
substrate_uniprot substrate_genes site source AM_pathogenicity substrate_sequence substrate_species sub_site substrate_phosphoseq position site_seq
0 A0A024R4G9 C19orf48 MGC13170 hCG_2008493 S20 psp NaN MTVLEAVLEIQAITGSRLLSMVPGPARPPGSCWDPTQCTRTWLLSH... Homo sapiens (Human) A0A024R4G9_S20 MTVLEAVLEIQAITGSRLLsMVPGPARPPGSCWDPTQCTRTWLLSH... 20 _MTVLEAVLEIQAITGSRLLsMVPGPARPPGSCWDPTQCTR
1 A0A075B6Q4 None S24 ochoa NaN MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... Homo sapiens (Human) A0A075B6Q4_S24 MDIQKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKT... 24 QKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPG
2 A0A075B6Q4 None S35 ochoa NaN MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... Homo sapiens (Human) A0A075B6Q4_S35 MDIQKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKT... 35 EDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKTHRAIADHLF
3 A0A075B6Q4 None S57 ochoa NaN MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... Homo sapiens (Human) A0A075B6Q4_S57 MDIQKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKT... 57 EDCMSVPGKTHRAIADHLFWsEETKSRFTEYsMTssVMRRN
4 A0A075B6Q4 None S68 ochoa NaN MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... Homo sapiens (Human) A0A075B6Q4_S68 MDIQKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKT... 68 RAIADHLFWsEETKSRFTEYsMTssVMRRNEQLTLHDERFE 
check_seq_df(df.head(),'site_seq')
0    _MTVLEAVLEIQAITGSRLLsMVPGPARPPGSCWDPTQCTR
1    QKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPG
2    EDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKTHRAIADHLF
3    EDCMSVPGKTHRAIADHLFWsEETKSRFTEYsMTssVMRRN
4    RAIADHLFWsEETKSRFTEYsMTssVMRRNEQLTLHDERFE
Name: site_seq, dtype: object

source

validate_site

 validate_site (site_info, seq)

Validate site position residue match with site residue.

site='S610'
seq = 'MSVPSSLSQSAINANSHGGPALSLPLPLHAAHNQLLNAKLQATAVGPKDLRSAMGEGGGPEPGPANAKWLKEGQNQLRRAATAHRDQNRNVTLTLAEEASQEPEMAPLGPKGLIHLYSELELSAHNAANRGLRGPGLIISTQEQGPDEGEEKAAGEAEEEEEDDDDEEEEEDLSSPPGLPEPLESVEAPPRPQALTDGPREHSKSASLLFGMRNSAASDEDSSWATLSQGSPSYGSPEDTDSFWNPNAFETDSDLPAGWMRVQDTSGTYYWHIPTGTTQWEPPGRASPSQGSSPQEESQLTWTGFAHGEGFEDGEFWKDEPSDEAPMELGLKEPEEGTLTFPAQSLSPEPLPQEEEKLPPRNTNPGIKCFAVRSLGWVEMTEEELAPGRSSVAVNNCIRQLSYHKNNLHDPMSGGWGEGKDLLLQLEDETLKLVEPQSQALLHAQPIISIRVWGVGRDSGRERDFAYVARDKLTQMLKCHVFRCEAPAKNIATSLHEICSKIMAERRNARCLVNGLSLDHSKLVDVPFQVEFPAPKNELVQKFQVYYLGNVPVAKPVGVDVINGALESVLSSSSREQWTPSHVSVAPATLTILHQQTEAVLGECRVRFLSFLAVGRDVHTFAFIMAAGPASFCCHMFWCEPNAASLSEAVQAACMLRYQKCLDARSQASTSCLPAPPAESVARRVGWTVRRGVQSLWGSLKPKRLGAHTP'
validate_site(site,seq)
1

source

validate_site_df

 validate_site_df (df, site_info_col, protein_seq_col)

Validate site position residue match with site residue in a dataframe.

validate_site_df(df.head(),'site','substrate_sequence')
0    1
1    1
2    1
3    1
4    1
dtype: int64

Phosphorylate protein seq

source

phosphorylate_seq

 phosphorylate_seq (seq, *sites)

Phosphorylate protein sequence based on phosphosites (e.g.,S140).

Type Details
seq full protein sequence
sites VAR_POSITIONAL site info, e.g., S140 
seq = 'MSKSESPKEPEQLRKLFIGGLSFETTDESLRSHFEQWGTLTDCVVMRDPNTKRSRGFGFVTYATVEEVDAAMNARPHKVDGRVVEPKRAVSREDSQRPDAHLTVKKIFVGGIKEDTEEHHLRDYFEQYGKIEVIEIMTDRGSGKKRGFAFVTFDDHDSVDKIVIQKYHTVNGHNCEVRKALSKQEMASASSSQRGRSGSGNFGGGRGGGFGGNDNFGRGGNFSGRGGFGGSRGGGGYGGSGDGYNGFGNDGSNFGGGGSYNDFGNYNNQSSNFGPMKGGNFEGRSSGPHGGGGQYFAKPRNQGGYGGSSSSSSYGSGRRF'
phosphorylate_seq(seq,*['S95', 'S22', 'T25', 'S6', 'S158'])
'MSKSEsPKEPEQLRKLFIGGLsFEtTDESLRSHFEQWGTLTDCVVMRDPNTKRSRGFGFVTYATVEEVDAAMNARPHKVDGRVVEPKRAVSREDsQRPDAHLTVKKIFVGGIKEDTEEHHLRDYFEQYGKIEVIEIMTDRGSGKKRGFAFVTFDDHDsVDKIVIQKYHTVNGHNCEVRKALSKQEMASASSSQRGRSGSGNFGGGRGGGFGGNDNFGRGGNFSGRGGFGGSRGGGGYGGSGDGYNGFGNDGSNFGGGGSYNDFGNYNNQSSNFGPMKGGNFEGRSSGPHGGGGQYFAKPRNQGGYGGSSSSSSYGSGRRF'

source

phosphorylate_seq_df

 phosphorylate_seq_df (df, id_col='substrate_uniprot',
                       seq_col='substrate_sequence', site_col='site')

Phosphorylate whole sequence based on phosphosites in a dataframe

Type Default Details
df
id_col str substrate_uniprot column of sequence ID
seq_col str substrate_sequence column that contains protein sequence
site_col str site column that contains site info, e.g., S140 
df=Data.get_human_site()
df.head()
substrate_uniprot substrate_genes site source AM_pathogenicity substrate_sequence substrate_species sub_site substrate_phosphoseq position site_seq
0 A0A024R4G9 C19orf48 MGC13170 hCG_2008493 S20 psp NaN MTVLEAVLEIQAITGSRLLSMVPGPARPPGSCWDPTQCTRTWLLSH... Homo sapiens (Human) A0A024R4G9_S20 MTVLEAVLEIQAITGSRLLsMVPGPARPPGSCWDPTQCTRTWLLSH... 20 _MTVLEAVLEIQAITGSRLLsMVPGPARPPGSCWDPTQCTR
1 A0A075B6Q4 None S24 ochoa NaN MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... Homo sapiens (Human) A0A075B6Q4_S24 MDIQKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKT... 24 QKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPG
2 A0A075B6Q4 None S35 ochoa NaN MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... Homo sapiens (Human) A0A075B6Q4_S35 MDIQKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKT... 35 EDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKTHRAIADHLF
3 A0A075B6Q4 None S57 ochoa NaN MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... Homo sapiens (Human) A0A075B6Q4_S57 MDIQKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKT... 57 EDCMSVPGKTHRAIADHLFWsEETKSRFTEYsMTssVMRRN
4 A0A075B6Q4 None S68 ochoa NaN MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... Homo sapiens (Human) A0A075B6Q4_S68 MDIQKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKT... 68 RAIADHLFWsEETKSRFTEYsMTssVMRRNEQLTLHDERFE 
phosphorylate_seq_df(df.head(100),'substrate_uniprot','substrate_sequence','site')
substrate_uniprot site substrate_sequence phosphoseq
0 A0A024R4G9 [S20] MTVLEAVLEIQAITGSRLLSMVPGPARPPGSCWDPTQCTRTWLLSH... MTVLEAVLEIQAITGSRLLsMVPGPARPPGSCWDPTQCTRTWLLSH...
1 A0A075B6Q4 [S24, S35, S57, S68, S71, S72] MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... MDIQKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKT...
... ... ... ... ...
22 A0A0A6YYL6 [S5, Y139, S141, S142] MVRYSLDPENPTKSCKSRGSNLRVHFKNTRETAQAIKGMHIRKATK... MVRYsLDPENPTKSCKSRGSNLRVHFKNTRETAQAIKGMHIRKATK...
23 A0A0B4J1R7 [T6, S43, S45, S46] MMATGTPESQARFGQSVKGLLTEKVTTCGTDVIALTKQVLKGSRSS... MMATGtPESQARFGQSVKGLLTEKVTTCGTDVIALTKQVLKGsRss...

24 rows × 4 columns

Extract site seq

source

extract_site_seq

 extract_site_seq (df:pandas.core.frame.DataFrame, seq_col:str,
                   site_col:str, n=7)

Extract -n to +n site sequence from protein sequence

Type Default Details
df DataFrame dataframe that contains protein sequence
seq_col str column name of protein sequence
site_col str column name of site information (e.g., S10)
n int 7 length of surrounding sequence (default -7 to +7)

As some datasets only contains protein information and position of phosphorylation sites, but not phosphorylation site sequence, we can retreive protein sequence and use this function to get -7 to +7 phosphorylation site sequence (as numpy array).

Remember to validate the phospho-acceptor at position 0 before extract the site sequence, as there could be mismatch due to the protein sequence database updates.

df.head()
substrate_uniprot substrate_genes site source AM_pathogenicity substrate_sequence substrate_species sub_site substrate_phosphoseq position site_seq
0 A0A024R4G9 C19orf48 MGC13170 hCG_2008493 S20 psp NaN MTVLEAVLEIQAITGSRLLSMVPGPARPPGSCWDPTQCTRTWLLSH... Homo sapiens (Human) A0A024R4G9_S20 MTVLEAVLEIQAITGSRLLsMVPGPARPPGSCWDPTQCTRTWLLSH... 20 _MTVLEAVLEIQAITGSRLLsMVPGPARPPGSCWDPTQCTR
1 A0A075B6Q4 None S24 ochoa NaN MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... Homo sapiens (Human) A0A075B6Q4_S24 MDIQKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKT... 24 QKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPG
2 A0A075B6Q4 None S35 ochoa NaN MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... Homo sapiens (Human) A0A075B6Q4_S35 MDIQKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKT... 35 EDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKTHRAIADHLF
3 A0A075B6Q4 None S57 ochoa NaN MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... Homo sapiens (Human) A0A075B6Q4_S57 MDIQKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKT... 57 EDCMSVPGKTHRAIADHLFWsEETKSRFTEYsMTssVMRRN
4 A0A075B6Q4 None S68 ochoa NaN MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... Homo sapiens (Human) A0A075B6Q4_S68 MDIQKSENEDDSEWEDVDDEKGDsNDDYDSAGLLsDEDCMSVPGKT... 68 RAIADHLFWsEETKSRFTEYsMTssVMRRNEQLTLHDERFE 
extract_site_seq(df.head(),
                 seq_col='substrate_sequence',
                 site_col='site',
                 n=30
                 )
100%|██████████| 5/5 [00:00<00:00, 4705.30it/s]
array(['___________MTVLEAVLEIQAITGSRLLSMVPGPARPPGSCWDPTQCTRTWLLSHTPRR',
       '_______MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKTHRAIADHL',
       'KSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKTHRAIADHLFWSEETKSRFT',
       'DYDSAGLLSDEDCMSVPGKTHRAIADHLFWSEETKSRFTEYSMTSSVMRRNEQLTLHDERF',
       'DCMSVPGKTHRAIADHLFWSEETKSRFTEYSMTSSVMRRNEQLTLHDERFEKFYEQYDDDE'],
      dtype='<U61')

End