Get kinase-specific PSSMs

from katlas.core import *
import pandas as pd

df = Data.get_ks_dataset()

CPU times: user 878 ms, sys: 338 ms, total: 1.22 s
Wall time: 5.63 s

df['kinase_id'] = df['kinase_uniprot'] + '_' + df['kinase_protein'].str.split().str[0]

cnt = df['kinase_id'].value_counts()

idx = cnt[cnt>=40].index
idx

Index(['P12931_SRC', 'P29320_EPHA3', 'P07332_FES', 'Q16288_NTRK3',
       'Q9UM73_ALK', 'P00519_ABL1', 'P36888_FLT3', 'P29322_EPHA8',
       'P29323_EPHB2', 'P54762_EPHB1',
       ...
       'P35626_GRK3', 'Q99640_PKMYT1', 'Q6P2M8_CAMK1B', 'O00311_CDC7',
       'Q9NYV4_CDK12', 'Q15746_SMMLCK', 'Q01973_ROR1', 'P15056_BRAF',
       'Q6P0Q8_MAST2', 'O14976_GAK'],
      dtype='object', name='kinase_id', length=333)

df.shape

(187066, 22)

We only evaluate those on kinome tree

df = df[df['kinase_id'].isin(idx)].copy()

df.shape

(185883, 22)

df['site_seq_upper']=df.site_seq.str.upper()

df['source_len'] = df.source.str.split('|').str.len()

def get_LO_all(pssms,site_type='STY'):
    out=[]
    for idx, flat_pssm in pssms.iterrows():
        out.append(flatten_pssm(get_pssm_LO_flat(flat_pssm,site_type)))
    return pd.DataFrame(out,index=pssms.index)

Take out 20% of PSP as test

psp = df[df.source.str.contains('PSP')].copy()

def sample(group):
    n = max(1, int(len(group) * 0.2))  # At least 1 row if group is small
    # weights = group['source_len'].values
    # weights = weights / weights.sum()  # normalize

    sampled = group.sample(
        n=n, replace=False, random_state=42
    )

    # Add back the group key as a column
    sampled['kinase_uniprot'] = group.name
    return sampled

test = psp.groupby('kinase_uniprot', group_keys=False)\
    .apply(sample,include_groups=False)

test.kinase_group.value_counts()

kinase_group
CMGC        777
AGC         511
TK          387
CAMK        357
Atypical    148
Other       108
STE          89
CK1          63
TKL          44
NEK          16
Name: count, dtype: int64

test

	kin_sub_site	substrate_uniprot	site	source	substrate_genes	substrate_phosphoseq	position	site_seq	sub_site	substrate_sequence	...	kinase_family	kinase_subfamily	kinase_pspa_big	kinase_pspa_small	kinase_coral_ID	num_kin	kinase_id	site_seq_upper	source_len	kinase_uniprot
160	O00141_P46527_T157	P46527	T157	SIGNOR\|EPSD\|PSP	CDKN1B KIP1 p27	MSNVRVSNGsPsLERMDARQAEHPKPSACRNLFGPVDHEELTRDLE...	157	PsDsQTGLAEQCAGIRKRPAtDDSSTQNKRANRTEENVsDG	P46527_T157	MSNVRVSNGSPSLERMDARQAEHPKPSACRNLFGPVDHEELTRDLE...	...	SGK	SGK	Basophilic	Akt/rock	SGK1	6	O00141_SGK1	PSDSQTGLAEQCAGIRKRPATDDSSTQNKRANRTEENVSDG	3	O00141
309	O00141_Q96J92_S1217	Q96J92	S1217	EPSD\|PSP	WNK4 PRKWNK4	MLASPATETTVLMSQTEADLALRPPPPLGTAGQPRLGPPPRRARRF...	1217	SRRNsLQRSEPPGPGIMRRNsLsGsSTGSQEQRASKGVTFA	Q96J92_S1217	MLASPATETTVLMSQTEADLALRPPPPLGTAGQPRLGPPPRRARRF...	...	SGK	SGK	Basophilic	Akt/rock	SGK1	1	O00141_SGK1	SRRNSLQRSEPPGPGIMRRNSLSGSSTGSQEQRASKGVTFA	2	O00141
369	O00141_Q9UN36_S346	Q9UN36	S346	EPSD\|PSP	NDRG2 KIAA1248 SYLD	MAELQEVQITEEKPLLPGQTPEAAKEAELAARILLDQGQTHSVETP...	346	sRsRtAsLtsAAsVDGNRsRsRtLsQssEsGtLsSGPPGHT	Q9UN36_S346	MAELQEVQITEEKPLLPGQTPEAAKEAELAARILLDQGQTHSVETP...	...	SGK	SGK	Basophilic	Akt/rock	SGK1	1	O00141_SGK1	SRSRTASLTSAASVDGNRSRSRTLSQSSESGTLSSGPPGHT	2	O00141
39	O00141_O60343_T642	O60343	T642	GPS6\|PSP	TBC1D4 AS160 KIAA0603	MEPPSCIQDEPFPHPLEPEPGVSAQPGPGKPSDKRFRLWYVGGSCL...	642	AWQTFPEEDSDSPQFRRRAHtFsHPPsstKRKLNLQDGRAQ	O60343_T642	MEPPSCIQDEPFPHPLEPEPGVSAQPGPGKPSDKRFRLWYVGGSCL...	...	SGK	SGK	Basophilic	Akt/rock	SGK1	4	O00141_SGK1	AWQTFPEEDSDSPQFRRRAHTFSHPPSSTKRKLNLQDGRAQ	2	O00141
314	O00141_Q96PU5_S448	Q96PU5	S448	GPS6\|SIGNOR\|ELM\|EPSD\|PSP	NEDD4L KIAA0439 NEDL3	MATGLGEPVYGLsEDEGESRILRVKVVSGIDLAKKDIFGASDPYVK...	448	sATNSNNHLIEPQIRRPRsLssPtVTLSAPLEGAKDsPVRR	Q96PU5_S448	MATGLGEPVYGLSEDEGESRILRVKVVSGIDLAKKDIFGASDPYVK...	...	SGK	SGK	Basophilic	Akt/rock	SGK1	4	O00141_SGK1	SATNSNNHLIEPQIRRPRSLSSPTVTLSAPLEGAKDSPVRR	5	O00141
...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...
185492	Q9Y4K4_P49841_S9	P49841	S9	SIGNOR\|EPSD\|PSP	GSK3B	MSGRPRttsFAEsCKPVQQPsAFGsMKVSRDKDGSKVTTVVAtPGQ...	9	____________MSGRPRttsFAEsCKPVQQPsAFGsMKVS	P49841_S9	MSGRPRTTSFAESCKPVQQPSAFGSMKVSRDKDGSKVTTVVATPGQ...	...	STE20	KHS	Map4k	Map4k	KHS1	25	Q9Y4K4_KHS1	____________MSGRPRTTSFAESCKPVQQPSAFGSMKVS	3	Q9Y4K4
185874	Q9Y5S2_O43255_S6	O43255	S6	PSP	SIAH2	MSRPsstGPsANKPCsKQPPPQPQHtPsPAAPPAAATISAAGPGSS...	6	_______________MSRPsstGPsANKPCsKQPPPQPQHt	O43255_S6	MSRPSSTGPSANKPCSKQPPPQPQHTPSPAAPPAAATISAAGPGSS...	...	DMPK	GEK	Basophilic	Akt/rock	MRCKb	1	Q9Y5S2_MRCKB	_______________MSRPSSTGPSANKPCSKQPPPQPQHT	1	Q9Y5S2
186807	Q9Y6E0_Q9Y2K2_T221	Q9Y2K2	T221	PSP	SIK3 KIAA0999 QSK L19	MAAAAASGAGGAAGAGTGGAGPAGRLLPPPAPGSPAAPAAVSPAAG...	221	NIKIADFGFSNLFTPGQLLKtWCGSPPYAAPELFEGKEYDG	Q9Y2K2_T221	MAAAAASGAGGAAGAGTGGAGPAGRLLPPPAPGSPAAPAAVSPAAG...	...	STE20	YSK	Map4k	Map4k	MST3	5	Q9Y6E0_MST3	NIKIADFGFSNLFTPGQLLKTWCGSPPYAAPELFEGKEYDG	1	Q9Y6E0
186392	Q9Y6E0_P57059_T182	P57059	T182	PSP	SIK1 SIK SNF1LK	MVIMSEFSADPAGQGQGQQKPLRVGFYDIERTLGKGNFAVVKLARH...	182	DIKLADFGFGNFYKSGEPLStWCGsPPYAAPEVFEGKEYEG	P57059_T182	MVIMSEFSADPAGQGQGQQKPLRVGFYDIERTLGKGNFAVVKLARH...	...	STE20	YSK	Map4k	Map4k	MST3	3	Q9Y6E0_MST3	DIKLADFGFGNFYKSGEPLSTWCGSPPYAAPEVFEGKEYEG	1	Q9Y6E0
186845	Q9Y6M4_O75581_S1490	O75581	S1490	PSP	LRP6	MGAVLRSLLACSFCVLLRAAPLLLYANRRDLRLVDATNGKENATIV...	1490	SSSSssTKGtYFPAILNPPPsPAtERsHYTMEFGYSsNsPs	O75581_S1490	MGAVLRSLLACSFCVLLRAAPLLLYANRRDLRLVDATNGKENATIV...	...	CK1	CK1	Acidophilic	Ck1	CK1g3	12	Q9Y6M4_CK1G3	SSSSSSTKGTYFPAILNPPPSPATERSHYTMEFGYSSNSPS	1	Q9Y6M4

2500 rows × 24 columns

test.to_parquet('out/CDDM_test_set.parquet')

test.head()

	kin_sub_site	substrate_uniprot	site	source	substrate_genes	substrate_phosphoseq	position	site_seq	sub_site	substrate_sequence	...	kinase_family	kinase_subfamily	kinase_pspa_big	kinase_pspa_small	kinase_coral_ID	num_kin	kinase_id	site_seq_upper	source_len	kinase_uniprot
160	O00141_P46527_T157	P46527	T157	SIGNOR\|EPSD\|PSP	CDKN1B KIP1 p27	MSNVRVSNGsPsLERMDARQAEHPKPSACRNLFGPVDHEELTRDLE...	157	PsDsQTGLAEQCAGIRKRPAtDDSSTQNKRANRTEENVsDG	P46527_T157	MSNVRVSNGSPSLERMDARQAEHPKPSACRNLFGPVDHEELTRDLE...	...	SGK	SGK	Basophilic	Akt/rock	SGK1	6	O00141_SGK1	PSDSQTGLAEQCAGIRKRPATDDSSTQNKRANRTEENVSDG	3	O00141
309	O00141_Q96J92_S1217	Q96J92	S1217	EPSD\|PSP	WNK4 PRKWNK4	MLASPATETTVLMSQTEADLALRPPPPLGTAGQPRLGPPPRRARRF...	1217	SRRNsLQRSEPPGPGIMRRNsLsGsSTGSQEQRASKGVTFA	Q96J92_S1217	MLASPATETTVLMSQTEADLALRPPPPLGTAGQPRLGPPPRRARRF...	...	SGK	SGK	Basophilic	Akt/rock	SGK1	1	O00141_SGK1	SRRNSLQRSEPPGPGIMRRNSLSGSSTGSQEQRASKGVTFA	2	O00141
369	O00141_Q9UN36_S346	Q9UN36	S346	EPSD\|PSP	NDRG2 KIAA1248 SYLD	MAELQEVQITEEKPLLPGQTPEAAKEAELAARILLDQGQTHSVETP...	346	sRsRtAsLtsAAsVDGNRsRsRtLsQssEsGtLsSGPPGHT	Q9UN36_S346	MAELQEVQITEEKPLLPGQTPEAAKEAELAARILLDQGQTHSVETP...	...	SGK	SGK	Basophilic	Akt/rock	SGK1	1	O00141_SGK1	SRSRTASLTSAASVDGNRSRSRTLSQSSESGTLSSGPPGHT	2	O00141
39	O00141_O60343_T642	O60343	T642	GPS6\|PSP	TBC1D4 AS160 KIAA0603	MEPPSCIQDEPFPHPLEPEPGVSAQPGPGKPSDKRFRLWYVGGSCL...	642	AWQTFPEEDSDSPQFRRRAHtFsHPPsstKRKLNLQDGRAQ	O60343_T642	MEPPSCIQDEPFPHPLEPEPGVSAQPGPGKPSDKRFRLWYVGGSCL...	...	SGK	SGK	Basophilic	Akt/rock	SGK1	4	O00141_SGK1	AWQTFPEEDSDSPQFRRRAHTFSHPPSSTKRKLNLQDGRAQ	2	O00141
314	O00141_Q96PU5_S448	Q96PU5	S448	GPS6\|SIGNOR\|ELM\|EPSD\|PSP	NEDD4L KIAA0439 NEDL3	MATGLGEPVYGLsEDEGESRILRVKVVSGIDLAKKDIFGASDPYVK...	448	sATNSNNHLIEPQIRRPRsLssPtVTLSAPLEGAKDsPVRR	Q96PU5_S448	MATGLGEPVYGLSEDEGESRILRVKVVSGIDLAKKDIFGASDPYVK...	...	SGK	SGK	Basophilic	Akt/rock	SGK1	4	O00141_SGK1	SATNSNNHLIEPQIRRPRSLSSPTVTLSAPLEGAKDSPVRR	5	O00141

5 rows × 24 columns

df.shape

(185883, 24)

df_eval = df[~df.index.isin(test.index)]

df_eval.shape

(183383, 24)

Get eval PSSMs

pssms = get_cluster_pssms(df_eval,
                          cluster_col = 'kinase_id',
                          count_thr=None, # since we already filtered, we set None here
                          valid_thr=None)

100%|███████████████████████████████████████████████████████████████████████████| 333/333 [00:11<00:00, 30.25it/s]

pssms.shape

(333, 943)

pssms_upper = get_cluster_pssms(df_eval,
                                     seq_col='site_seq_upper',
                          cluster_col = 'kinase_id',
                          count_thr=None, # since we already filtered, we set None here
                          valid_thr=None)

100%|███████████████████████████████████████████████████████████████████████████| 333/333 [00:11<00:00, 29.50it/s]

LO of eval PSSMs

LO = get_LO_all(pssms)

LO_upper = get_LO_all(pssms_upper,'STY_upper')

LO.shape

(333, 943)

Remove isoform and pseudo gene

info= Data.get_kinase_info()

info = info[info.pseudo=='0'].copy()

info['id'] = info.uniprot+'_'+info.kinase

LO[~LO.index.isin(info.id)]

	-20P	-20G	-20A	-20C	-20S	-20T	-20V	-20I	-20L	-20M	...	20H	20K	20R	20Q	20N	20D	20E	20pS	20pT	20pY
P07948-2_LYN	-0.695061	0.248942	-0.181606	-0.523522	-0.241880	-0.087184	0.270835	0.248626	-0.177055	0.151905	...	-1.002663	0.187090	-0.131176	-0.477873	0.089392	-0.069890	0.272381	-0.624875	-0.293957	0.686397
O60566_BUB1B	-0.098063	0.177522	0.006417	-2.364642	-0.336759	-0.656228	0.622357	0.285512	-1.214575	-1.313708	...	0.538365	0.313082	-0.184508	-1.521805	0.314920	0.267606	0.993983	-0.586346	-0.015962	-0.647041
P05771-2_PKCB	-0.513296	0.082197	-0.419347	0.153007	0.387344	0.446387	1.033094	1.359558	-0.959957	-0.059090	...	1.086193	-0.296631	-0.264711	-1.710942	0.415289	0.443465	0.117313	0.283410	-0.205099	-0.099214
Q13976-2_PKG1	0.267160	-0.880855	0.326552	-20.552054	-0.980098	-0.599127	0.959565	-0.422922	-0.420509	-0.841570	...	0.565165	0.388792	0.076757	0.183066	-0.243242	-0.843097	-0.192211	0.440454	-1.311089	1.379757

4 rows × 943 columns

LO = LO[LO.index.isin(info.id)]
LO_upper =LO_upper[LO_upper.index.isin(info.id)]

pssms= pssms[pssms.index.isin(info.id)]
pssms_upper = pssms_upper[pssms_upper.index.isin(info.id)]

LO.shape,pssms.shape

((329, 943), (329, 943))

pssms.to_parquet('out/CDDM_pssms_eval_psp_02.parquet')
pssms_upper.to_parquet('out/CDDM_pssms_eval_upper_psp_02.parquet')

LO.to_parquet('out/CDDM_pssms_LO_eval_psp_02.parquet')
LO_upper.to_parquet('out/CDDM_pssms_LO_eval_upper_psp_02.parquet')