library(GAMBLR)

library(tidyverse)

setwd("/projects/rmorin/projects/gambl-repos/gambl-kdreval/")

pathologies <- c("DLBCL", "FL", "CLL", "BL")

metadata <- get_gambl_metadata(seq_type_filter = "genome") %>%

    filter(pathology %in% pathologies)

generate_table <- function(

    this_meta,

    projection = "grch37"

){

    maf <- get_ssm_by_samples(

        these_samples_metadata = this_meta,

        projection = projection,

        subset_from_merge = TRUE

    )

    if(projection == "grch37"){

        regions <- grch37_ashm_regions %>%

            mutate(

                chr_name = gsub("chr", "", chr_name)

            )

    }else{

        regions <- hg38_ashm_regions

    }

    annotated <- cool_overlaps(

        maf,

        regions %>%

            mutate(

                name = paste(gene, region, sep = "_")

            ),

        columns2 = colnames(regions)[1:3]

    )

    mutated_counts <- annotated %>%

        count(

            gene, name, Tumor_Sample_Barcode

        )

    pathology_counts <- metadata %>%

        select(Tumor_Sample_Barcode, pathology) %>%

        group_by(pathology) %>%

        mutate(total = n()) %>%

        ungroup

    all_counts <- left_join(

        mutated_counts,

        pathology_counts

    )

    all_counts <- all_counts %>%

        group_by(pathology, name) %>%

        mutate(mut = n()) %>%

        ungroup %>%

        select(-c(Tumor_Sample_Barcode, n)) %>%

        distinct

    all_counts <- all_counts %>%

        mutate(pc = round((mut/total)*100, 2)) %>%

        pivot_wider(

            names_from = pathology,

            names_glue = "{pathology}_{.value}",

            values_from = c(total, mut, pc)

        ) %>% select(-gene)

    output <- left_join(

        regions %>%

            mutate(

                name = paste(gene, region, sep = "_")

            ) %>%

            select(all_of(c("name", colnames(regions)[1:3]))),

        all_counts

    ) %>%

        replace_na(

            list(

                DLBCL_total = pull(unique(pathology_counts[pathology_counts$pathology=="DLBCL", "total"])),

                FL_total = pull(unique(pathology_counts[pathology_counts$pathology=="FL", "total"])),

                CLL_total = pull(unique(pathology_counts[pathology_counts$pathology=="CLL", "total"])),

                BL_total = pull(unique(pathology_counts[pathology_counts$pathology=="BL", "total"]))

            )

        ) %>%

        replace(is.na(.), 0)

    output <- output %>%

        select(

            name,

            colnames(regions)[1:3],

            contains("DLBCL"),

            contains("FL"),

            contains("CLL"),

            contains("BL")

        )

}

grch37_table <- generate_table(

    this_meta = metadata

)

hg38_table <- generate_table(

    this_meta = metadata,

    projection = "hg38"

)

write_tsv(

    grch37_table,

    "~/my_dir/repos/LLMPP/resources/curated/somatic_hypermutation_locations_with_DLBCL_frequencies_grch37.tsv"

)

write_tsv(

    hg38_table,

    "~/my_dir/repos/LLMPP/resources/curated/somatic_hypermutation_locations_with_DLBCL_frequencies_hg38.tsv"

)