## 2 Methods
### The Genomic Data Format  
For genomic data, we use a free-BED data representation, in which fix coordinate fields (chromosome, start position, end position, strand) and we include additional fields according to the specific type of experiment; for every data type we provide a specific ready-to-use schema in XML format. We implemented automatic procedures for converting the original GDC genomic data into such free-BED format; to index our BED output files, we introduce _opengdc_id_, an extension of the aliquot Universal Unique Identifier (UUID, that is the unit of analysis for GDC genomic data identifying a sample analyzed portion). Since in the GDC an aliquot relates to different data types, _opengdc_id_ concatenates the _aliquot__uuid_ with the specific _data type_. In the following, we provide an overview of the input and output data of our standardization procedures; for a detailed description of all input and output fields of each data type, the reader may refer to the OpenGDC Format Definition (Supplementary File 1). _Gene Expression Quantification_ data are provided in the GDC for each aliquot in three tab-delimited files, each of which presents the Ensembl ID of the gene and one of the following values:  
1. _FPKM_, the number of Fragments Per Kilobase of transcript per Million mapped reads;
2. _FPKM-UQ_, the Upper Quartile normalized FPKM value;
3. _counts_, the number of reads aligned to each gene, calculated by HT-Seq. We merge the content of these files using the common _Gene_Ensembl_ field. Then, we extract additional information to describe the gene regions. In the final free-BED structure we include the genomic coordinates (i.e., _chromosome, start position, end position_ and _strand_), the _gene_symbol_ from GENCODE (human genome version GRCh38 annotation), and the corresponding _entrez_gene_id_ from the NCBI genome annotation. _MiRNA Expression Quantification_ data are derived from the sequencing of the micro RNA (i.e., miRNA). They contain information about the nucleotide sequence and the expression of miRNAs. One file per aliquot is provided by the GDC, where each row refers to a single miRNA and contains its expression computed on all reads aligning to that particular miRNA. In the free-BED output we consider all fields provided in input, with the addition of the miRNA genomic coordinates extracted from miRBase and the corresponding _entrez_gene_id_ and _gene_symbol_ extracted from HGNC. _Isoform Expression Quantification_ data contain expression profiles calculated for each isoform of the miRNA sequence. The GDC provides one file for each aliquot, where each row refers to a single isoform. For the free-BED structure, all input fields are left unchanged with the exception of the _isoform_coords_ field, which is parsed to obtain separate genomic coordinate fields. As an addition, we retrieve the corresponding _entrez_gene_id_ and _gene_symbol_ from HGNC. A copy number variation (CNV) is a variation in the number of copies of a given genomic segment per cell. The GDC provides two data types related to CNVs: _Copy Number Segment_ (including both germline and somatic CNVs) and _Masked Copy Number Segment_ (including only somatic CNVs). The internal representation is the same for both data types. A single experiment is represented by a tab-delimited file, where each row refers to a single CNV. For the free-BED representation we reuse all input fields except for the sample id; we add the _strand_ field--required for the BED standard--which we always set to 'unknown' using the wildcard character ''. _Masked Somatic Mutation_ experiments discover mutations by aligning DNA sequences derived from tumor samples to sequences derived from normal samples and to a reference sequence.