# Dash app to visualize scRNA-seq data quality control metrics from scanpy objects
# Shoutout to Coding-with-Adam for the initial template of the project: 
# https://github.com/Coding-with-Adam/Dash-by-Plotly/blob/master/Dash%20Components/Graph/dash-graph.py

import dash
from dash import dcc, html, Output, Input, callback
import plotly.express as px
import dash_callback_chain
import yaml
import polars as pl
import os
from natsort import natsorted
#pl.enable_string_cache(False)

dash.register_page(__name__, location="sidebar")

dataset = "datasuture/pbs/Suture_polars"

# Set custom resolution for plots:
config_fig = {
  'toImageButtonOptions': {
    'format': 'svg',
    'filename': 'custom_image',
    'height': 600,
    'width': 700,
    'scale': 1,
  }
}
from adlfs import AzureBlobFileSystem
mountpount=os.environ['AZURE_MOUNT_POINT'],
AZURE_STORAGE_ACCESS_KEY=os.getenv('AZURE_STORAGE_ACCESS_KEY')
AZURE_STORAGE_ACCOUNT=os.getenv('AZURE_STORAGE_ACCOUNT')

# Load in config file
config_path = "./data/config.yaml"

# Add the read-in data from the yaml file
def read_config(filename):
    with open(filename, 'r') as yaml_file:
        config = yaml.safe_load(yaml_file)
    return config

config = read_config(config_path)
path_parquet = config.get("path_parquet")
col_batch = config.get("col_batch")
col_features = config.get("col_features")
col_counts = config.get("col_counts")
col_mt = config.get("col_mt")

#filepath = f"az://{path_parquet}"

storage_options={'account_name': AZURE_STORAGE_ACCOUNT, 'account_key': AZURE_STORAGE_ACCESS_KEY} #, 'anon': False
#azfs = AzureBlobFileSystem(**storage_options )

# Load in multiple dataframes
df = pl.scan_parquet(f"az://{dataset}.parquet", storage_options=storage_options).collect()

# Create the second tab content with scatter-plot_db1-5 and scatter-plot_db1-6
tab2_content = html.Div([
    html.Div([
            html.Label("S-cycle genes"),
            dcc.Dropdown(id='dpdn3', value="Mcm5", multi=False,
                 options=[
    "Cdc45",
    "Uhrf1",
    "Mcm2",
    "Slbp",
    "Mcm5",
    "Pola1",
    "Gmnn",
    "Cdc6",
    "Rrm2",
    "Atad2",
    "Dscc1",
    "Mcm4",
    "Chaf1b",
    "Rfc2",
    "Msh2",
    "Fen1",
    "Hells",
    "Prim1",
    "Tyms",
    "Mcm6",
    "Wdr76",
    "Rad51",
    "Pcna",
    "Ccne2",
    "Casp8ap2",
    "Usp1",
    "Nasp",
    "Rpa2",
    "Ung",
    "Rad51ap1",
    "Blm",
    "Pold3",
    "Rrm1",
    "Cenpu",
    "Gins2",
    "Tipin",
    "Brip1",
    "Dtl",
    "Exo1",
    "Ubr7",
    "Clspn",
    "E2f8",
    "Cdca7"
]),
            html.Label("G2M-cycle genes"),
            dcc.Dropdown(id='dpdn4', value="Top2a", multi=False,
                 options=[
    "Ube2c",
    "Lbr",
    "Ctcf",
    "Cdc20",
    "Cbx5",
    "Kif11",
    "Anp32e",
    "Birc5",
    "Cdk1",
    "Tmpo",
    "Hmmr",
    "Pimreg",
    "Aurkb",
    "Top2a",
    "Gtse1",
    "Rangap1",
    "Cdca3",
    "Ndc80",
    "Kif20b",
    "Cenpf",
    "Nek2",
    "Nuf2",
    "Nusap1",
    "Bub1",
    "Tpx2",
    "Aurka",
    "Ect2",
    "Cks1b",
    "Kif2c",
    "Cdca8",
    "Cenpa",
    "Mki67",
    "Ccnb2",
    "Kif23",
    "Smc4",
    "G2e3",
    "Tubb4b",
    "Anln",
    "Tacc3",
    "Dlgap5",
    "Ckap2",
    "Ncapd2",
    "Ttk",
    "Ckap5",
    "Cdc25c",
    "Hjurp",
    "Cenpe",
    "Ckap2l",
    "Cdca2",
    "Hmgb2",
    "Cks2",
    "Psrc1",
    "Gas2l3"
]),
    ]),
    html.Div([
        dcc.Graph(id='scatter-plot_db1-5', figure={}, className='three columns',config=config_fig)
    ]),
    html.Div([
        dcc.Graph(id='scatter-plot_db1-6', figure={}, className='three columns',config=config_fig)
    ]),
    html.Div([
        dcc.Graph(id='scatter-plot_db1-7', figure={}, className='three columns',config=config_fig)
    ]),
    html.Div([
        dcc.Graph(id='scatter-plot_db1-8', figure={}, className='three columns',config=config_fig)
    ]),
])

# Create the second tab content with scatter-plot_db1-5 and scatter-plot_db1-6
tab3_content = html.Div([
    html.Div([
            html.Label("UMAP condition 1"),
            dcc.Dropdown(id='dpdn5', value="condition", multi=False,
                 options=df.columns),
            html.Label("UMAP condition 2"),
            dcc.Dropdown(id='dpdn6', value="Pax6", multi=False,
                 options=df.columns),
    html.Div([
        dcc.Graph(id='scatter-plot_db1-9', figure={}, className='four columns', hoverData=None ,config=config_fig)
    ]),
    html.Div([
        dcc.Graph(id='scatter-plot_db1-10', figure={}, className='four columns', hoverData=None, config=config_fig)
    ]),
    html.Div([
        dcc.Graph(id='scatter-plot_db1-11', figure={}, className='four columns',config=config_fig)
    ]),
    html.Div([
            dcc.Graph(id='my-graph_db12', figure={}, clickData=None, hoverData=None,
                  className='four columns',config=config_fig
                  )
    ]),
    ]),
])

tab4_content = html.Div([
     html.Label("Column chosen"),    
     dcc.Dropdown(id='dpdn2', value="cell states", multi=False,
                  options=df.columns),
    html.Div([
            html.Label("Multi gene"),
            dcc.Dropdown(id='dpdn7', value=["Pax6","Sox9","Cdk8","Il31ra","Gpha2",
                                            "Areg","Krt13","Krt19","Psca","Muc20",
                                            "S100a9","Lama3","Itgb4","Itga6","Thy1","Dcn","Scn7a",
                                            "Cdh19","Mpz","Ptprc","Cd52","Cd69","Cd86","Rgs5","Des","Myh11","Cd93","Pecam1",
                                            "Abcg2","Lyve1","Mki67"], multi=True,
                 options=df.columns),
]),
    html.Div([
        dcc.Graph(id='scatter-plot_db1-12', figure={}, className='row',style={'width': '100vh', 'height': '90vh'})
    ]),
])

# Define the tabs layout
layout = html.Div([
    html.H1(f'Dataset analysis dashboard: {dataset}'),
    dcc.Tabs(id='tabs', style= {'width': 600,
        'font-size': '100%',
        'height': 50}, value='tab1',children=[
        #dcc.Tab(label='Dataset', value='tab0', children=tab0_content),
        #dcc.Tab(label='QC', value='tab1', children=tab1_content),
        dcc.Tab(label='UMAP visualisation', value='tab3', children=tab3_content),
        dcc.Tab(label='Multi dot', value='tab4', children=tab4_content),
        dcc.Tab(label='Cell cycle', value='tab2', children=tab2_content),
    ]),
])

@callback(
    Output(component_id='scatter-plot_db1-5', component_property='figure'),
    Output(component_id='scatter-plot_db1-6', component_property='figure'),
    Output(component_id='scatter-plot_db1-7', component_property='figure'),
    Output(component_id='scatter-plot_db1-8', component_property='figure'),
    Output(component_id='scatter-plot_db1-9', component_property='figure'),
    Output(component_id='scatter-plot_db1-10', component_property='figure'),
    Output(component_id='scatter-plot_db1-11', component_property='figure'),
    Output(component_id='scatter-plot_db1-12', component_property='figure'),
    Output(component_id='my-graph_db12', component_property='figure'),
    Input(component_id='dpdn2', component_property='value'),
    Input(component_id='dpdn3', component_property='value'),
    Input(component_id='dpdn4', component_property='value'),
    Input(component_id='dpdn5', component_property='value'),
    Input(component_id='dpdn6', component_property='value'),
    Input(component_id='dpdn7', component_property='value'),
     
)

def update_graph_and_pie_chart(col_chosen, s_chosen, g2m_chosen, condition1_chosen, condition2_chosen, condition3_chosen): #, range_value_1, range_value_2, range_value_3 batch_chosen, 
    batch_chosen = df[col_chosen].unique().to_list()
    dff = df.filter(
        (pl.col(col_chosen).cast(str).is_in(batch_chosen)) #&
)
    # Select ordering of plots
    if condition1_chosen == "integrated_cell_states":
        cat_ord= {condition1_chosen: natsorted(dff[condition1_chosen].unique())}
    else:
        cat_ord= {condition1_chosen: natsorted(dff[condition1_chosen].unique())}

    # Calculate the mean expression
    
    # Melt wide format DataFrame into long format
    # Specify batch column as string type and gene columns as float type
    list_conds = condition3_chosen
    list_conds += [col_chosen]
    dff_pre = dff.select(list_conds)
    
    # Melt wide format DataFrame into long format
    dff_long = dff_pre.melt(id_vars=col_chosen, variable_name="Gene", value_name="Mean expression")
    
    # Calculate the mean expression levels for each gene in each region
    expression_means = dff_long.lazy().group_by([col_chosen, "Gene"]).agg(pl.mean("Mean expression")).collect() #
    
    # Calculate the percentage total expressed
    dff_long1 = dff_pre.melt(id_vars=col_chosen, variable_name="Gene")#.group_by(pl.all()).agg(pl.len())
    count = 1
    dff_long2 = dff_long1.with_columns(pl.lit(count).alias("len"))
    dff_long3 = dff_long2.filter(pl.col("value") > 0).group_by([col_chosen, "Gene"]).agg(pl.sum("len").alias("len"))
    dff_long4 = dff_long2.group_by([col_chosen, "Gene"]).agg(pl.sum("len").alias("total"))
    dff_5 = dff_long4.join(dff_long3, on=[col_chosen,"Gene"], how="outer")
    result = dff_5.select([
        pl.when((pl.col('len').is_not_null()) & (pl.col('total').is_not_null()))
              .then(pl.col('len') / pl.col('total')*100)
              .otherwise(None).alias("%"),
    ])
    result = result.with_columns(pl.col("%").fill_null(0))
    dff_5[["percentage"]] = result[["%"]]
    dff_5 = dff_5.select(pl.col(col_chosen,"Gene","percentage"))

    # Final part to join the percentage expressed and mean expression levels
    expression_means = expression_means.join(dff_5, on=[col_chosen,"Gene"], how="inner")
    
    fig_scatter_db1_5 = px.scatter(data_frame=dff, x='X_umap-0', y='X_umap-1', color=s_chosen,
                            labels={'X_umap-0': 'umap1' , 'X_umap-1': 'umap2'},
                            hover_name=None, title="S-cycle gene:",template="seaborn")

    fig_scatter_db1_6 = px.scatter(data_frame=dff, x='X_umap-0', y='X_umap-1', color=g2m_chosen,
                            labels={'X_umap-0': 'umap1' , 'X_umap-1': 'umap2'},
                            hover_name='condition', title="G2M-cycle gene:",template="seaborn")
    
    fig_scatter_db1_7 = px.scatter(data_frame=dff, x='X_umap-0', y='X_umap-1', color="S_score",
                            labels={'X_umap-0': 'umap1' , 'X_umap-1': 'umap2'},
                            hover_name='condition', title="S score:",template="seaborn")
    
    fig_scatter_db1_8 = px.scatter(data_frame=dff, x='X_umap-0', y='X_umap-1', color="G2M_score",
                            labels={'X_umap-0': 'umap1' , 'X_umap-1': 'umap2'},
                            hover_name='condition', title="G2M score:",template="seaborn")

    # Sort values of custom in-between
    dff = dff.sort(condition1_chosen)
    
    fig_scatter_db1_9 = px.scatter(data_frame=dff, x='X_umap-0', y='X_umap-1', color=condition1_chosen,
                            labels={'X_umap-0': 'umap1' , 'X_umap-1': 'umap2'},
                            hover_name=None,hover_data = None, template="seaborn",category_orders=cat_ord)
    fig_scatter_db1_9.update_traces(hoverinfo='none', hovertemplate=None)
    fig_scatter_db1_9.update_layout(hovermode=False)
    
    fig_scatter_db1_10 = px.scatter(data_frame=dff, x='X_umap-0', y='X_umap-1', color=condition2_chosen,
                            labels={'X_umap-0': 'umap1' , 'X_umap-1': 'umap2'},
                            hover_name='condition',template="seaborn")
    
    fig_scatter_db1_11 = px.scatter(data_frame=dff, x=condition1_chosen, y=condition2_chosen, color=condition1_chosen,
                            #labels={'X_umap-0': 'umap1' , 'X_umap-1': 'umap2'},
                            hover_name='condition',template="seaborn",category_orders=cat_ord)

    # Reorder categories on natural sorting or on the integrated cell state order of the paper
    if col_chosen == "integrated_cell_states":
        fig_scatter_db1_12 = px.scatter(data_frame=expression_means, x="Gene", y=col_chosen, color="Mean expression",
                                    size="percentage", size_max = 20,
                                #labels={'X_umap-0': 'umap1' , 'X_umap-1': 'umap2'},
                                hover_name=col_chosen,template="seaborn",category_orders={col_chosen: natsorted(expression_means[col_chosen].unique())})
    else:                                                                                
        fig_scatter_db1_12 = px.scatter(data_frame=expression_means, x="Gene", y=col_chosen, color="Mean expression",
                                    size="percentage", size_max = 20,
                                #labels={'X_umap-0': 'umap1' , 'X_umap-1': 'umap2'},
                                hover_name=col_chosen,template="seaborn",category_orders={col_chosen: natsorted(expression_means[col_chosen].unique()),"Gene": condition3_chosen})
    
    fig_violin_db12 = px.violin(data_frame=dff, x=condition1_chosen, y=condition2_chosen, box=True, points="all",
                            color=condition1_chosen, hover_name=condition1_chosen,template="seaborn",category_orders=cat_ord)


    return fig_scatter_db1_5, fig_scatter_db1_6, fig_scatter_db1_7, fig_scatter_db1_8, fig_scatter_db1_9, fig_scatter_db1_10, fig_scatter_db1_11, fig_scatter_db1_12, fig_violin_db12