nextflow.enable.dsl=2

//SYNTHEA
params.n_pat = 2//10 //number of patients to generate, must be => 2 (one male one female)
params.percent_male = 0.5 // between 0-1, percant of mail patients
//params.age = '18-80' //age range of the population, expressed as age-age
//params.state = '"District of Columbia"' //'Hawaii' //'Texas' //'Georgia'
//params.city = '' //'Washington' //'' //'Honolulu' //'Houston' //'Atlanta'
params.imputed_store =  '/mnt/Avatar/imputed/ukbb/imputed'  //'/rosalind/ukbb/imputed'
params.pheno_store = '/mnt/Avatar/dd/synthea/metadata/ukbb_phenotypes_filtered.csv'
params.disease = 'healthy' //'schizophrenia' //'healthy' //'leukaemia' //'leukaemia' //'Purpura and other haemorrhagic conditions' //['tongue cancer', 'dementia', 'arthritis'] //'tongue cancer' //'dementia' 
params.healthy_dir = '/Workspace/next/registry/pipelines/digital_patient' //'/mnt/Avatar/digital_patient' // data copy is here 
//params.n_var = 100
params.outdir = '/mnt/OmicNAS/dd/digital_patient'
//BORZOI
params.container_borzoi = 'borzoi:latest'
params.containerOptions = '--gpus all --rm -v /mnt:/mnt'
params.project_name = 'test'
params.mane = '/Workspace/next/registry/pipelines/digital_patient/MANE.GRCh38.v1.3.update.tsv'
//VCF2PROT
params.container_vcf2prot = "vcf2prot:latest"
//RNA2PROTEINEXPRESSION
params.container_rna2protexpression = 'rna2protexpression:latest'
params.containerOptions_rna2protexpression = '--gpus all --rm -v /mnt:/mnt -v /dbs:/dbs' 
//CORTO
params.container_corto = 'corto:latest'
params.regulon = '/Workspace/next/registry/pipelines/digital_patient/regulon.rda'
//CIBERSORT
params.cibersortx_username = "gabriel.richman.2009@anderson.ucla.edu" 
params.cibersortx_token = "b5b39e563fb947df4cfd4843d40fdb99"
params.container_ecotyper = 'ecotyper:latest'
params.signature_matrix = "/Workspace/next/registry/pipelines/digital_patient/LM22_sourceGEP_ensg.txt"
params.ecotyper_outdir = "/mnt/OmicNAS/olamide/ecotyper/results/ecotyper"


//SYNTHEA
include {get_disease_stats_no_patients} from './main_synthea.nf'
include {generate_m_variants_cudf} from './main_synthea.nf'
include {generate_f_variants_cudf} from './main_synthea.nf'
include {make_vcfs} from './main_synthea.nf'
include {generate_m_healthy_cudf} from './main_synthea.nf'
include {generate_f_healthy_cudf} from './main_synthea.nf'
//BORZOI
include {FILTER_VCF} from './main_borzoi.nf'
include {PREDICT_EXPRESSION} from './main_borzoi.nf'
include {CREATE_PROTEIN_CLUSTER} from './main_borzoi.nf'
//VCF2PROT
include {VCF2PROT} from './main_vcf2prot.nf'
//RNA2PROTEINEXPRESSION 
include {RNA2PROTEXPRESSION} from './main_rna2proteinexpression'
//CORTO
include {CORTO} from './main_corto.nf'
//CIBERSORT
include {CONVERT_TO_TXT} from './main_cibersortx.nf'
include {CIBERSORTx_FRACTIONS} from './main_cibersortx.nf'
include {CIBERSORTx_HIRES} from './main_cibersortx.nf'
include {ADD_TISSUE_NAMES_TO_CIBERSORTX} from './main_cibersortx.nf'

workflow {
  //SYNTHEA
  switch (params.disease) {
    case 'healthy':
      //healthy 
      generate_m_healthy_cudf(params.healthy_dir)
      generate_f_healthy_cudf(params.healthy_dir)
      m_healthy = generate_m_healthy_cudf.out
      f_healthy = generate_f_healthy_cudf.out
      txt_ch = f_healthy.mix(m_healthy).flatten()
      break 
    default:
      //disease
      get_disease_stats_no_patients()
      generate_m_variants_cudf(get_disease_stats_no_patients.out)
      generate_f_variants_cudf(get_disease_stats_no_patients.out)
      f_var = generate_f_variants_cudf.out
      m_var = generate_m_variants_cudf.out
      txt_ch = f_var.mix(m_var).flatten()
  }
  make_vcfs(txt_ch)
  //BORZOI
  // Prepare the VCF file(s)
  //vcf_ch = Channel.fromPath(make_vcfs.out)
  // THIS IS USES TO CREATE PROTEIN CLUSTER ON A SAME BORZOI INPUT AND SPLI ONES TO BIG FOR BORZOI (LEN = 524288)
  // THIS STEP NEEDS TO BR RUN TO CREATE DATA FOR NEXT STEP ONLY IF NEW REFERENCE/RNAS ARE GOING TO BE USE
  //CREATE_PROTEIN_CLUSTER(params.mane)
  FILTER_VCF(params.mane, make_vcfs.out)
  PREDICT_EXPRESSION(FILTER_VCF.out, params.mane)
  //VCF2PROT
  VCF2PROT(make_vcfs.out, FILTER_VCF.out)
  //RNA2PROTEINEXPRESSION
  //collect  is here onyl to stop RNA2PROTEXPRESSION run at the same time as BORZOI (not enough CUDA space)
  RNA2PROTEXPRESSION(PREDICT_EXPRESSION.out.collect())
  //CORTO
  CORTO(PREDICT_EXPRESSION.out, params.regulon)
  //CIBERSORT
  signature_file = Channel.fromPath(params.signature_matrix, checkIfExists: true)
  CONVERT_TO_TXT(PREDICT_EXPRESSION.out)
  CIBERSORTx_FRACTIONS(CONVERT_TO_TXT.out, signature_file)  
  CIBERSORTx_HIRES(CONVERT_TO_TXT.out, CIBERSORTx_FRACTIONS.out, signature_file)
  ADD_TISSUE_NAMES_TO_CIBERSORTX(CONVERT_TO_TXT.out, CIBERSORTx_HIRES.out)
}