Metadata-Version: 2.1
Name: python-katlas
Version: 0.0.4
Summary: tools for predicting kinome specificities
Home-page: https://github.com/sky1ove/python-katlas
Author: lily
Author-email: lcai888666@gmail.com
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# KATLAS


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<a target="_blank" href="https://colab.research.google.com/github/sky1ove/katlas/blob/main/nbs/index.ipynb">
<img src="https://colab.research.google.com/assets/colab-badge.svg" alt="Open In Colab"/>
</a>

<img alt="Katlas logo" width="700" caption="Katlas logo" src="https://github.com/sky1ove/katlas/raw/main/dataset/images/logo.png" id="logo"/>

KATLAS is a repository containing python tools to predict kinases given
a substrate sequence. It also contains datasets of kinase substrate
specificities and human phosphoproteomics.

***References***: Please cite the appropriate papers if KATLAS is
helpful to your research.

- KATLAS was described in the paper \[Decoding Human Kinome
  Specificities through a Computational Data-Driven Approach
  (manuscript)\]

- The positional scanning peptide array (PSPA) data is from paper [An
  atlas of substrate specificities for the human serine/threonine
  kinome](https://www.nature.com/articles/s41586-022-05575-3) and paper
  [The intrinsic substrate specificity of the human tyrosine
  kinome](https://www.nature.com/articles/s41586-024-07407-y)

- The kinase substrate datasets used for generating PSSMs are derived
  from
  [PhosphoSitePlus](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245126/)
  and paper [Large-scale Discovery of Substrates of the Human
  Kinome](https://www.nature.com/articles/s41598-019-46385-4)

- Phosphorylation sites are acquired from
  [PhosphoSitePlus](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245126/),
  paper [The functional landscape of the human
  phosphoproteome](https://www.nature.com/articles/s41587-019-0344-3),
  and [CPTAC](https://pdc.cancer.gov/pdc/cptac-pancancer) /
  [LinkedOmics](https://academic.oup.com/nar/article/46/D1/D956/4607804)

## Tutorials on Colab

- 1.  [Substrate scoring on a single substrate
      sequence](https://colab.research.google.com/github/sky1ove/katlas/blob/main/nbs/tutorial_01_sinlge_input.ipynb)
- 2.  [High throughput substrate scoring on phosphoproteomics
      dataset](https://colab.research.google.com/github/sky1ove/katlas/blob/main/nbs/tutorial_02_high_throughput.ipynb)
- 3.  [Query a protein’s phosphorylation sites and predict their
      upstream
      kinases](https://colab.research.google.com/github/sky1ove/katlas/blob/main/nbs/tutorial_03_query_gene.ipynb)
- 4.  [Kinase enrichment analysis for AKT
      inhibitor](https://colab.research.google.com/github/sky1ove/katlas/blob/main/nbs/tutorial_04a_enrichment_AKTi.ipynb)
      / [Kinase enrichment analysis for EGFR
      inhibitor](https://colab.research.google.com/github/sky1ove/katlas/blob/main/nbs/tutorial_04b_enrichment_EGFRi.ipynb)

## Install

Install the latest version through git

``` python
!pip install git+https://github.com/sky1ove/katlas.git -Uqq
```

## Import

``` python
from katlas.core import *
```

# Quick start

We provide two methods to calculate substrate sequence:

- Computational Data-Driven Method (CDDM)
- Positional Scanning Peptide Array (PSPA)

We consider the input in two formats:

- a single input string (phosphorylation site)
- a csv/dataframe that contains a column of phosphorylation sites

For input sequences, we also consider it in two conditions:

- all capital
- contains lower cases indicating phosphorylation status

## Single sequence as input

### CDDM, all capital

``` python
predict_kinase('AAAAAAASGGAGSDN',**param_CDDM_upper)
```

    considering string: ['-7A', '-6A', '-5A', '-4A', '-3A', '-2A', '-1A', '0S', '1G', '2G', '3A', '4G', '5S', '6D', '7N']

    kinase
    PAK6     2.032
    ULK3     2.032
    PRKX     2.012
    ATR      1.991
    PRKD1    1.988
             ...  
    DDR2     0.928
    EPHA4    0.928
    TEK      0.921
    KIT      0.915
    FGFR3    0.910
    Length: 289, dtype: float64

### CDDM, with lower case indicating phosphorylation status

``` python
predict_kinase('AAAAAAAsGGAGsDN',**param_CDDM)
```

    considering string: ['-7A', '-6A', '-5A', '-4A', '-3A', '-2A', '-1A', '0s', '1G', '2G', '3A', '4G', '5s', '6D', '7N']

    kinase
    ULK3     1.987
    PAK6     1.981
    PRKD1    1.946
    PIM3     1.944
    PRKX     1.939
             ...  
    EPHA4    0.905
    EGFR     0.900
    TEK      0.898
    FGFR3    0.894
    KIT      0.882
    Length: 289, dtype: float64

### PSPA, with lower case indicating phosphorylation status

``` python
predict_kinase('AEEKEyHsEGG',**param_PSPA).head()
```

    considering string: ['-5A', '-4E', '-3E', '-2K', '-1E', '0y', '1H', '2s', '3E', '4G', '5G']

    kinase
    EGFR     4.013
    FGFR4    3.568
    ZAP70    3.412
    CSK      3.241
    SYK      3.209
    dtype: float64

### To replicate the results from The Kinase Library (PSPA)

Check this link: [The Kinase
Library](https://kinase-library.phosphosite.org/site?s=AEEKEy*HsEGG&pp=false&scp=true),
and use log2(score) to rank, it shows same results with the below (with
slight differences due to rounding).

``` python
predict_kinase('AEEKEyHSEGG',**param_PSPA).head(10)
```

    considering string: ['-5A', '-4E', '-3E', '-2K', '-1E', '0y', '1H', '2S', '3E', '4G', '5G']

    kinase
    EGFR         3.181
    FGFR4        2.390
    CSK          2.308
    ZAP70        2.068
    SYK          1.998
    PDHK1_TYR    1.922
    RET          1.732
    MATK         1.688
    FLT1         1.627
    BMPR2_TYR    1.456
    dtype: float64

- So far [The kinase Library](https://kinase-library.phosphosite.org)
  considers all ***tyr sequences*** in capital regardless of whether or
  not they contain lower cases, which is a small bug and should be fixed
  soon.
- Kinase with “\_TYR” indicates it is a dual specificity kinase tested
  in PSPA tyrosine setting, which has not been included in
  kinase-library yet.

We can also calculate the percentile score using a referenced score
sheet.

``` python
# Percentile reference sheet
y_pct = Data.get_pspa_tyr_pct()

get_pct('AEEKEyHSEGG',**param_PSPA_y, pct_ref = y_pct)
```

    considering string: ['-5A', '-4E', '-3E', '-2K', '-1E', '0Y', '1H', '2S', '3E', '4G', '5G']



|       | log2(score) | percentile |
|-------|-------------|------------|
| EGFR  | 3.181       | 96.787423  |
| FGFR4 | 2.390       | 94.012303  |
| CSK   | 2.308       | 95.201640  |
| ZAP70 | 2.068       | 88.380041  |
| SYK   | 1.998       | 85.522898  |
| ...   | ...         | ...        |
| EPHA1 | -3.501      | 12.139440  |
| FES   | -3.699      | 21.216678  |
| TNK1  | -4.269      | 5.481887   |
| TNK2  | -4.577      | 2.050581   |
| DDR2  | -4.920      | 10.403281  |



## High-throughput substrate scoring on a dataframe

### Load your csv

``` python
# df = pd.read_csv('your_file.csv')
```

### Load a demo df

``` python
# Load a demo df with phosphorylation sites
df = Data.get_ochoa_site().head()
df.iloc[:,-2:]
```


|     | site_seq        | gene_site      |
|-----|-----------------|----------------|
| 0   | VDDEKGDSNDDYDSA | A0A075B6Q4_S24 |
| 1   | YDSAGLLSDEDCMSV | A0A075B6Q4_S35 |
| 2   | IADHLFWSEETKSRF | A0A075B6Q4_S57 |
| 3   | KSRFTEYSMTSSVMR | A0A075B6Q4_S68 |
| 4   | FTEYSMTSSVMRRNE | A0A075B6Q4_S71 |



### Set the column name and param to calculate

Here we choose param_CDDM_upper, as the sequences in the demo df are all
in capital. You can also choose other params.

``` python
results = predict_kinase_df(df,'site_seq',**param_CDDM_upper)
results
```

    input dataframe has a length 5
    Preprocessing
    Finish preprocessing
    Calculating position: [-7, -6, -5, -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 6, 7]

    100%|██████████| 289/289 [00:05<00:00, 56.64it/s]



| kinase | SRC      | EPHA3    | FES      | NTRK3    | ALK      | EPHA8    | ABL1     | FLT3     | EPHB2    | FYN      | ... | MEK5     | PKN2     | MAP2K7   | MRCKB    | HIPK3    | CDK8     | BUB1     | MEKK3    | MAP2K3   | GRK1     |
|--------|----------|----------|----------|----------|----------|----------|----------|----------|----------|----------|-----|----------|----------|----------|----------|----------|----------|----------|----------|----------|----------|
| 0      | 0.991760 | 1.093712 | 1.051750 | 1.067134 | 1.013682 | 1.097519 | 0.966379 | 0.982464 | 1.054986 | 1.055910 | ... | 1.314859 | 1.635470 | 1.652251 | 1.622672 | 1.362973 | 1.797155 | 1.305198 | 1.423618 | 1.504941 | 1.872020 |
| 1      | 0.910262 | 0.953743 | 0.942327 | 0.950601 | 0.872694 | 0.932586 | 0.846899 | 0.826662 | 0.915020 | 0.942713 | ... | 1.175454 | 1.402006 | 1.430392 | 1.215826 | 1.569373 | 1.716455 | 1.270999 | 1.195081 | 1.223082 | 1.793290 |
| 2      | 0.849866 | 0.899910 | 0.848895 | 0.879652 | 0.874959 | 0.899414 | 0.839200 | 0.836523 | 0.858040 | 0.867269 | ... | 1.408003 | 1.813739 | 1.454786 | 1.084522 | 1.352556 | 1.524663 | 1.377839 | 1.173830 | 1.305691 | 1.811849 |
| 3      | 0.803826 | 0.836527 | 0.800759 | 0.894570 | 0.839905 | 0.781001 | 0.847847 | 0.807040 | 0.805877 | 0.801402 | ... | 1.110307 | 1.703637 | 1.795092 | 1.469653 | 1.549936 | 1.491344 | 1.446922 | 1.055452 | 1.534895 | 1.741090 |
| 4      | 0.822793 | 0.796532 | 0.792343 | 0.839882 | 0.810122 | 0.781420 | 0.805251 | 0.795022 | 0.790380 | 0.864538 | ... | 1.062617 | 1.357689 | 1.485945 | 1.249266 | 1.456078 | 1.422782 | 1.376471 | 1.089629 | 1.121309 | 1.697524 |



## Phosphorylation sites

Besides calculating sequence scores, we also provides multiple datasets
of phosphorylation sites.

### CPTAC pan-cancer phosphoproteomics

``` python
df = Data.get_cptac_ensembl_site()
df.head(3)
```



|     | gene               | site  | site_seq        | protein           | gene_name | gene_site   | protein_site          |
|-----|--------------------|-------|-----------------|-------------------|-----------|-------------|-----------------------|
| 0   | ENSG00000003056.8  | S267  | DDQLGEESEERDDHL | ENSP00000000412.3 | M6PR      | M6PR_S267   | ENSP00000000412_S267  |
| 1   | ENSG00000003056.8  | S267  | DDQLGEESEERDDHL | ENSP00000440488.2 | M6PR      | M6PR_S267   | ENSP00000440488_S267  |
| 2   | ENSG00000048028.11 | S1053 | PPTIRPNSPYDLCSR | ENSP00000003302.4 | USP28     | USP28_S1053 | ENSP00000003302_S1053 |



### [Ochoa et al. human phosphoproteome](https://www.nature.com/articles/s41587-019-0344-3)

``` python
df = Data.get_ochoa_site()
df.head(3)
```


|     | uniprot    | position | residue | is_disopred | disopred_score | log10_hotspot_pval_min | isHotspot | uniprot_position | functional_score | current_uniprot | name             | gene | Sequence                                          | is_valid | site_seq        | gene_site      |
|-----|------------|----------|---------|-------------|----------------|------------------------|-----------|------------------|------------------|-----------------|------------------|------|---------------------------------------------------|----------|-----------------|----------------|
| 0   | A0A075B6Q4 | 24       | S       | True        | 0.91           | 6.839384               | True      | A0A075B6Q4_24    | 0.149257         | A0A075B6Q4      | A0A075B6Q4_HUMAN | None | MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... | True     | VDDEKGDSNDDYDSA | A0A075B6Q4_S24 |
| 1   | A0A075B6Q4 | 35       | S       | True        | 0.87           | 9.192622               | False     | A0A075B6Q4_35    | 0.136966         | A0A075B6Q4      | A0A075B6Q4_HUMAN | None | MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... | True     | YDSAGLLSDEDCMSV | A0A075B6Q4_S35 |
| 2   | A0A075B6Q4 | 57       | S       | False       | 0.28           | 0.818834               | False     | A0A075B6Q4_57    | 0.125364         | A0A075B6Q4      | A0A075B6Q4_HUMAN | None | MDIQKSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKT... | True     | IADHLFWSEETKSRF | A0A075B6Q4_S57 |



### PhosphoSitePlus human phosphorylation site

``` python
df = Data.get_psp_human_site()
df.head(3)
```


|     | gene  | protein     | uniprot | site | gene_site | SITE_GRP_ID | species | site_seq              | LT_LIT | MS_LIT | MS_CST | CST_CAT# | Ambiguous_Site |
|-----|-------|-------------|---------|------|-----------|-------------|---------|-----------------------|--------|--------|--------|----------|----------------|
| 0   | YWHAB | 14-3-3 beta | P31946  | T2   | YWHAB_T2  | 15718712    | human   | \_\_\_\_\_\_MtMDksELV | NaN    | 3.0    | 1.0    | None     | 0              |
| 1   | YWHAB | 14-3-3 beta | P31946  | S6   | YWHAB_S6  | 15718709    | human   | \_\_MtMDksELVQkAk     | NaN    | 8.0    | NaN    | None     | 0              |
| 2   | YWHAB | 14-3-3 beta | P31946  | Y21  | YWHAB_Y21 | 3426383     | human   | LAEQAERyDDMAAAM       | NaN    | NaN    | 4.0    | None     | 0              |



### Unique sites of combined Ochoa & PhosphoSitePlus

``` python
df = Data.get_combine_site_psp_ochoa()
df.head(3)
```


|     | site_seq        | gene_site  | gene  | source | num_site | acceptor | -7  | -6  | -5  | -4  | ... | -2  | -1  | 0   | 1   | 2   | 3   | 4   | 5   | 6   | 7   |
|-----|-----------------|------------|-------|--------|----------|----------|-----|-----|-----|-----|-----|-----|-----|-----|-----|-----|-----|-----|-----|-----|-----|
| 0   | AAAAAAASGGAGSDN | PBX1_S136  | PBX1  | ochoa  | 1        | S        | A   | A   | A   | A   | ... | A   | A   | S   | G   | G   | A   | G   | S   | D   | N   |
| 1   | AAAAAAASGGGVSPD | PBX2_S146  | PBX2  | ochoa  | 1        | S        | A   | A   | A   | A   | ... | A   | A   | S   | G   | G   | G   | V   | S   | P   | D   |
| 2   | AAAAAAASGVTTGKP | CLASR_S349 | CLASR | ochoa  | 1        | S        | A   | A   | A   | A   | ... | A   | A   | S   | G   | V   | T   | T   | G   | K   | P   |



## Phosphorylation site sequence example

***All capital - 15 length (-7 to +7)***

- QSEEEKLSPSPTTED
- TLQHVPDYRQNVYIP
- TMGLSARyGPQFTLQ

***All capital - 10 length (-5 to +4)***

- SRDPHYQDPH
- LDNPDyQQDF
- AAAAAsGGAG

***With lowercase - (-7 to +7)***

- QsEEEKLsPsPTTED
- TLQHVPDyRQNVYIP
- TMGLsARyGPQFTLQ

***With lowercase - (-5 to +4)***

- sRDPHyQDPH
- LDNPDyQQDF
- AAAAAsGGAG
