Basic information ----------------------------------------------------------------------------------------------------------------- Date of creation: April 28, 2017 ^M Version: BioMuta 3.0^M Record number: Varies by table^M Number of associated tables: 10^M ^M ^M Summary^M -------------------------------------------------------------------------------------------------------------------^M These tables were generated as part of the supporting information to accompany submission of the manuscript titled "Loss and Gain of N-linked Glycosylation Sequons due to Single-nucleotide Variation in Cancer." This manuscript describes the workflow for identifying all possible N-linked glycosylation (NLG) sequons (Table S1), quantification of sequons and nonsynonymous single-nucleotide variations (nsSNVs) in various genes (Table S2), nsSNVs expected to cause loss of glycosylation (LOG) or gain of glycosylation (GOG) sequon in the somatic dataset (Tables S3 and S5, respectively), nsSNVs mapping to germline variants from the LOG and GOG datasets (Table S4 and S6, respectively), the subset of LOG and GOG variants that appear ONLY in the somatic data (Tables S7 and S8, respectively), and the subset of somatic-only LOG and GOG variants that appear across at least three cancer types (Tables S9 and S10, respectively). ^M ^M Variants were retrieved from BioMuta version 3.0 and Human Build 149 of dbSNP and mapped to NLGs using custom scripts as described in the manuscript (in review). ^M ^M ^M Table and column description ^M ------------------------------------------------------------------------------------------------------------------ ^M ^M ^M ^M TABLE S1. Nonredundant sequons^M ^M This table contains 59,341 NLGs identified by one of three methods: high-confidence NLGs (previously reported in databases with accompanying validated evidence or manual assertion tags), NLGs predicted by NetNGlyc (http://www.cbs.dtu.dk/services/NetNGlyc/), and custom scripts to identify all NXS/T (X!=P) sequons by string search.^M ^M Column name Description^M ================ ==================================================================================^M UniProtKB_AC UniProtKB/Swiss-Prot Accession ^M Gene_name Gene name^M Protein_name Protein name as reported by UniProt^M Sequence_Length Length of protein in amino acids^M Signal_Peptide_Existence Describes if a signal peptide is reported for that protein in UniProt^M Signal_Peptide_Position Reports the annotated signal peptide position if Signal_Peptide_Existence is "Y"^M Cellular_component Relevant cellular component keyword(s) associated with the protein in UniProt^M Motif_position Position of the "N" in the identified NXS/T sequon^M Subsequence Four-residue sequence about the NXS/T sequon beginning with the "N"^M Methods Identification method(s) used to find a given sequon in a given protein^M Domain Domain mapping to the position, if reported^M Secondary_Structure Secondary structure mapping to the position, if reported^M NetNGlyc_Prediction Likelihood of actual glycosylation at the sequon, as reported by NetNGlyc^M ^M ^M asic information ----------------------------------------------------------------------------------------------------------------- Date of creation: April 28, 2017 Version: BioMuta 3.0 Record number: Varies by table Number of associated tables: 10 Summary ------------------------------------------------------------------------------------------------------------------- These tables were generated as part of the supporting information to accompany submission of the manuscript titled "Loss and Gain of N-linked Glycosylation Sequons due to Single-nucleotide Variation in Cancer." This manuscript describes the workflow for identifying all possible N-linked glycosylation (NLG) sequons (Table S1), quantification of sequons and nonsynonymous single-nucleotide variations (nsSNVs) in various genes (Table S2), nsSNVs expected to cause loss of glycosylation (LOG) or gain of glycosylation (GOG) sequon in the somatic dataset (Tables S3 and S5, respectively), nsSNVs mapping to germline variants from the LOG and GOG datasets (Table S4 and S6, respectively), the subset of LOG and GOG variants that appear ONLY in the somatic data (Tables S7 and S8, respectively), and the subset of somatic-only LOG and GOG variants that appear across at least three cancer types (Tables S9 and S10, respectively). Variants were retrieved from BioMuta version 3.0 and Human Build 149 of dbSNP and mapped to NLGs using custom scripts as described in the manuscript (in review). Table and column description ------------------------------------------------------------------------------------------------------------------ TABLE S1. Nonredundant sequons This table contains 59,341 NLGs identified by one of three methods: high-confidence NLGs (previously reported in databases with accompanying validated evidence or manual assertion tags), NLGs predicted by NetNGlyc (http://www.cbs.dtu.dk/services/NetNGlyc/), and custom scripts to identify all NXS/T (X!=P) sequons by string search. Column name Description ================ ================================================================================== UniProtKB_AC UniProtKB/Swiss-Prot Accession Gene_name Gene name Protein_name Protein name as reported by UniProt Sequence_Length Length of protein in amino acids Signal_Peptide_Existence Describes if a signal peptide is reported for that protein in UniProt Signal_Peptide_Position Reports the annotated signal peptide position if Signal_Peptide_Existence is "Y" Cellular_component Relevant cellular component keyword(s) associated with the protein in UniProt Motif_position Position of the "N" in the identified NXS/T sequon Subsequence Four-residue sequence about the NXS/T sequon beginning with the "N" Methods Identification method(s) used to find a given sequon in a given protein Domain Domain mapping to the position, if reported Secondary_Structure Secondary structure mapping to the position, if reported NetNGlyc_Prediction Likelihood of actual glycosylation at the sequon, as reported by NetNGlyc TABLE S2. Counts This table is organized by each of the 16,169 proteins containing the 59,341 NLGs identified in Table S1. Counts of different characteristics including expected effect (loss or gain), high-confidence criteria, and prediction method are reported. Column name Description ================ ================================================================================== UniProtKB_AC UniProtKB/Swiss-Prot Accession Gene_name Gene name Protein_name Protein name as reported by UniProt Sequence_Length Length of protein in amino acids Signal_Peptide_Existence Describes if a signal peptide is reported for that protein in UniProt Signal_Peptide_Position Reports the annotated signal peptide position if Signal_Peptide_Existence is "Y" Cellular_component Relevant cellular component keyword(s) associated with the protein in UniProt High_Confidence_Sequon Number of sequons reported by databases with associated validated evidence or manual assertion tags NetNGlyc_Predicted_Sequon Number of sequons reported by NetNGlyc String_Search_Sequon Number of sequons reported by custom string search LOG_somatic_only_HC_sequon Number of high-confidence sequons in somatic-only LOG dataset LOG_somatic_only_NetNGlyc_sequon Number of NetNGlyc sequons in somatic-only LOG dataset LOG_somatic_only_SS_sequon Number of string search sequons in somatic-only LOG dataset GOG_somatic_only_sequon Number of sequons predicted in somatic-only GOG dataset Count_by_length_total Count of total sequons in the protein normalized by the protein length Count_by_length_LOG_HC Count of high-confidence LOG sequons normalized by protein length Count_by_length_GOG_HC Count of high-confidence GOG sequons normalized by protein length Residues_per_NLG_total Spacing of total NLG sequons reported by the number of residues per occurrence of NLG Residues_per_NLG_LOG_HC Spacing of high-confidence NLG sequons in the LOG dataset reported by the number of residues per occurrence of NLG Residues_per_NLG_GOG_HC Spacing of high-confidence NLG sequons in the GOG dataset reported by the number of residues per occurrence of NLG TABLE S3. LOG_all_somatic This table contains 10,807 somatic variants mapping to an NLG position and predicted to cause a loss of the consensus NXS/T motif at that position. These variants include all somatic variants reported by primary cancer sources regardless of germline variants occurring at the same positions. Column name Description ================ ================================================================================== UniProtKB_AC UniProtKB/Swiss-Prot Accession Gene_name Gene name Protein_name Protein name as reported by UniProt Sequence_Length Length of protein in amino acids Signal_Peptide_Existence Describes if a signal peptide is reported for that protein in UniProt Signal_Peptide_Position Reports the annotated signal peptide position if Signal_Peptide_Existence is "Y" Cellular_component Relevant cellular component keyword(s) associated with the protein in UniProt Motif_position Position of the "N" in the identified NXS/T sequon Subsequence Four-residue sequence about the NXS/T sequon beginning with the "N" Method Identification method(s) used to find a given sequon in a given protein Domain Domain mapping to the position, if reported Secondary_Structure Secondary structure mapping to the position, if reported NetNGlyc_Prediction Likelihood of actual glycosylation at the sequon, as reported by NetNGlyc Mutation_Position Position of the altered residue Reference Reference amino acid Variation Altered amino acid resulting from nsSNV Genomic_Variation Position of nucleotide variation within the coding frame Minor_Allele_Frequency MAF retrieved through Annovar during annotation associated with that position Source_Freq Frequency of samples containing this variant call by source PolyPhen2_Prediction Functional prediction reported by PolyPhen2 software; can be possibly damaging, probably damaging, or benign Cancer_Type Disease ontology ID (DOID) and label of cancers associated with samples containing this variant Data_Source Primary source of data from which variant calls were obtained Patient_ID Patient ID from primary source, when available PMID PubMed article ID for associated literature, when available HGMD_Disease Diseases associated with this variant in HGMD, when available HGMD_PMID PubMed article ID corresponding to publication reporting disease association in HGMD, when available TABLE S4. LOG_all_germline This table contains 37,498 germline variants mapping to an NLG and predicted to cause a loss of the consensus NXS/T motif. These variants include ONLY germline nsSNVs reported by dbSNP that map to identified NLG positions and cause a loss of the NLG sequon. Column name Description ================ ================================================================================== UniProtKB_AC UniProtKB/Swiss-Prot Accession Gene_name Gene name Protein_name Protein name as reported by UniProt Sequence_Length Length of protein in amino acids Signal_Peptide_Existence Describes if a signal peptide is reported for that protein in UniProt Signal_Peptide_Position Reports the annotated signal peptide position if Signal_Peptide_Existence is "Y" Cellular_component Relevant cellular component keyword(s) associated with the protein in UniProt Motif_position Position of the "N" in the identified NXS/T sequon Subsequence Four-residue sequence about the NXS/T sequon beginning with the "N" Method Identification method(s) used to find a given sequon in a given protein Domain Domain mapping to the position, if reported Secondary_Structure Secondary structure mapping to the position, if reported NetNGlyc_Prediction Likelihood of actual glycosylation at the sequon, as reported by NetNGlyc Chr Chromosome reported by dbSNP vcf Start Start position reported by dbSNP vcf; for SNVs, start and end positions will be the same End End position reported by dbSNP vcf; for SNVs, start and end positions will be the same Ref Reference nucleotide Alt Varied nucleotide Func.refGene RefSeq function retrieved through Annovar; all should be exonic Gene.refGene RefSeq gene name corresponding to the chromosome position retrieved through Annovar GeneDetail.refGene Additional RefSeq gene information retrieved through Annovar, when available ExonicFunc.refGene Functional impact of exonic variants retrieved through Annovar; all should be nonsynonymous SNV AAChange.refGene Corresponding amino acid change resulting from variant retrieved through Annovar mRNA accession RefSeq accession for mRNA transcript mapping to variant reported by dbSNP protein accession RefSeq accession for protein sequence mapping to variant reported by dbSNP RefAA Reference amino acid encoded by position reported by dbSNP AAPos Amino acid position encoded by variant position reported by dbSNP AltAA Altered amino acid encoded by varant at position reported by dbSNP VCFInfo Additional information from original dbSNP vcf HGMD_Disease Diseases associated with this variant in HGMD, when available HGMD_PMID PubMed article ID corresponding to publication reporting disease association in HGMD, when available TABLE S5. GOG_all_somatic This table contains 15,675 somatic variants predicted to cause a gain of the consensus NXS/T motif at that position. These variants include all somatic variants reported by primary cancer sources regardless of germline variants occurring at the same positions. Column name Description ================ ================================================================================== UniProtKB_AC UniProtKB/Swiss-Prot Accession Gene_name Gene name Protein_name Protein name as reported by UniProt Sequence_Length Length of protein in amino acids Signal_Peptide_Existence Describes if a signal peptide is reported for that protein in UniProt Signal_Peptide_Position Reports the annotated signal peptide position if Signal_Peptide_Existence is "Y" Cellular_component Relevant cellular component keyword(s) associated with the protein in UniProt Motif_position Position of the "N" in the identified NXS/T sequon Subsequence Four-residue sequence about the NXS/T sequon beginning with the "N" Prediction Predicted effect of variant; all should be gain_of_glycosylation Domain Domain mapping to the position, if reported Secondary_Structure Secondary structure mapping to the position, if reported Mutation_Position Position of the altered residue Reference Reference amino acid Variation Altered amino acid resulting from nsSNV Genomic_Variation Position of nucleotide variation within the coding frame Minor_Allele_Frequency MAF retrieved through Annovar during annotation associated with that position in dbSNP Source_Freq Frequency of samples containing this variant call by source PolyPhen2_Prediction Functional prediction reported by PolyPhen2 software; can be possibly damaging, probably damaging, or benign Cancer_Type Disease ontology ID (DOID) and label of cancers associated with samples containing this variant Data_Source Primary source of data from which variant calls were obtained Patient_ID Patient ID from primary source, when available PMID PubMed article ID for associated literature, when available HGMD_Disease Diseases associated with this variant in HGMD, when available HGMD_PMID PubMed article ID corresponding to publication reporting disease association in HGMD, when available netGlycMotif Four-residue sequence including NXS/T motif reported by NetNGlyc netGlycPrediction Likelihood of actual glycosylation at the sequon, as reported by NetNGlyc TABLE S6. GOG_all_germline This table contains 39.455 germline variants predicted to cause a gain of the consensus NXS/T motif. These variants include ONLY germline nsSNVs reported by dbSNP that cause a gain of the NLG sequon. Column name Description ================ ================================================================================== UniProtKB_AC UniProtKB/Swiss-Prot Accession Gene_name Gene name Protein_name Protein name as reported by UniProt Sequence_Length Length of protein in amino acids Signal_Peptide_Existence Describes if a signal peptide is reported for that protein in UniProt Signal_Peptide_Position Reports the annotated signal peptide position if Signal_Peptide_Existence is "Y" Cellular_component Relevant cellular component keyword(s) associated with the protein in UniProt Motif_position Position of the "N" in the identified NXS/T sequon Subsequence Four-residue sequence about the NXS/T sequon beginning with the "N" Prediction Predicted effect of variant; all should be gain_of_glycosylation Domain Domain mapping to the position, if reported Secondary_Structure Secondary structure mapping to the position, if reported Chr Chromosome reported by dbSNP vcf Start Start position reported by dbSNP vcf; for SNVs, start and end positions will be the same End End position reported by dbSNP vcf; for SNVs, start and end positions will be the same Ref Reference nucleotide Alt Varied nucleotide Func.refGene RefSeq function retrieved through Annovar; all should be exonic Gene.refGene RefSeq gene name corresponding to the chromosome position retrieved through Annovar GeneDetail.refGene Additional RefSeq gene information retrieved through Annovar, when available ExonicFunc.refGene Functional impact of exonic variants retrieved through Annovar; all should be nonsynonymous SNV AAChange.refGene Corresponding amino acid change resulting from variant retrieved through Annovar mRNA accession RefSeq accession for mRNA transcript mapping to variant reported by dbSNP protein accession RefSeq accession for protein sequence mapping to variant reported by dbSNP RefAA Reference amino acid encoded by position reported by dbSNP AAPos Amino acid position encoded by variant position reported by dbSNP AltAA Altered amino acid encoded by varant at position reported by dbSNP VCFInfo Additional information from original dbSNP vcf HGMD_Disease Diseases associated with this variant in HGMD, when available HGMD_PMID PubMed article ID corresponding to publication reporting disease association in HGMD, when available NetNGlycmotif Four-residue sequence including NXS/T motif reported by NetNGlyc NetNGlycPrediction Likelihood of actual glycosylation at the sequon, as reported by NetNGlyc TABLE S7. LOG_somatic_only This table contains 8,895 somatic variants mapping to an NLG position and predicted to cause a loss of the consensus NXS/T motif at that position. These variants include ONLY those somatic variants WITHOUT germline variants occurring at the same positions. Column name Description ================ ================================================================================== UniProtKB_AC UniProtKB/Swiss-Prot Accession Gene_name Gene name Protein_name Protein name as reported by UniProt Sequence_Length Length of protein in amino acids Signal_Peptide_Existence Describes if a signal peptide is reported for that protein in UniProt Signal_Peptide_Position Reports the annotated signal peptide position if Signal_Peptide_Existence is "Y" Cellular_component Relevant cellular component keyword(s) associated with the protein in UniProt Motif_position Position of the "N" in the identified NXS/T sequon Subsequence Four-residue sequence about the NXS/T sequon beginning with the "N" Method Identification method(s) used to find a given sequon in a given protein Domain Domain mapping to the position, if reported Secondary_Structure Secondary structure mapping to the position, if reported NetNGlyc_Prediction Likelihood of actual glycosylation at the sequon, as reported by NetNGlyc Mutation_Position Position of the altered residue Reference Reference amino acid Variation Altered amino acid resulting from nsSNV Genomic_Variation Position of nucleotide variation within the coding frame Minor_Allele_Frequency MAF retrieved through Annovar during annotation associated with that position Source_Freq Frequency of samples containing this variant call by source PolyPhen2_Prediction Functional prediction reported by PolyPhen2 software; can be possibly damaging, probably damaging, or benign Cancer_Type Disease ontology ID (DOID) and label of cancers associated with samples containing this variant Data_Source Primary source of data from which variant calls were obtained Patient_ID Patient ID from primary source, when available PMID PubMed article ID for associated literature, when available HGMD_Disease Diseases associated with this variant in HGMD, when available HGMD_PMID PubMed article ID corresponding to publication reporting disease association in HGMD, when available TABLE S8. GOG_somatic_only This table contains 15,675 somatic variants predicted to cause a gain of the consensus NXS/T motif at that position. These variants include ONLY somatic variants reported by primary cancer sources WITHOUT germline variants occurring at the same positions. Column name Description ================ ================================================================================== UniProtKB_AC UniProtKB/Swiss-Prot Accession Gene_name Gene name Protein_name Protein name as reported by UniProt Sequence_Length Length of protein in amino acids Signal_Peptide_Existence Describes if a signal peptide is reported for that protein in UniProt Signal_Peptide_Position Reports the annotated signal peptide position if Signal_Peptide_Existence is "Y" Cellular_component Relevant cellular component keyword(s) associated with the protein in UniProt Motif_position Position of the "N" in the identified NXS/T sequon Subsequence Four-residue sequence about the NXS/T sequon beginning with the "N" Prediction Predicted effect of variant; all should be gain_of_glycosylation Domain Domain mapping to the position, if reported Secondary_Structure Secondary structure mapping to the position, if reported Mutation_Position Position of the altered residue Reference Reference amino acid Variation Altered amino acid resulting from nsSNV Genomic_Variation Position of nucleotide variation within the coding frame Minor_Allele_Frequency MAF retrieved through Annovar during annotation associated with that position in dbSNP Source_Freq Frequency of samples containing this variant call by source PolyPhen2_Prediction Functional prediction reported by PolyPhen2 software; can be possibly damaging, probably damaging, or benign Cancer_Type Disease ontology ID (DOID) and label of cancers associated with samples containing this variant Data_Source Primary source of data from which variant calls were obtained Patient_ID Patient ID from primary source, when available PMID PubMed article ID for associated literature, when available HGMD_Disease Diseases associated with this variant in HGMD, when available HGMD_PMID PubMed article ID corresponding to publication reporting disease association in HGMD, when available NetNGlycMotif Four-residue sequence including NXS/T motif reported by NetNGlyc NetNGlycPrediction Likelihood of actual glycosylation at the sequon, as reported by NetNGlyc TABLE S9. LOG_som_three_cancers This table contains 13 somatic variants mapping to an NLG position and predicted to cause a loss of the consensus NXS/T motif at that position in at least three different cancer types. These variants include ONLY those somatic variants WITHOUT germline variants occurring at the same positions occurring in three or more cancers. Column name Description ================ ================================================================================== UniProtKB_AC UniProtKB/Swiss-Prot Accession Gene_name Gene name Protein_name Protein name as reported by UniProt Sequence_Length Length of protein in amino acids Signal_Peptide_Existence Describes if a signal peptide is reported for that protein in UniProt Signal_Peptide_Position Reports the annotated signal peptide position if Signal_Peptide_Existence is "Y" Cellular_component Relevant cellular component keyword(s) associated with the protein in UniProt Motif_position Position of the "N" in the identified NXS/T sequon Subsequence Four-residue sequence about the NXS/T sequon beginning with the "N" Method Identification method(s) used to find a given sequon in a given protein Domain Domain mapping to the position, if reported Secondary_Structure Secondary structure mapping to the position, if reported NetNGlyc_Prediction Likelihood of actual glycosylation at the sequon, as reported by NetNGlyc Mutation_Position Position of the altered residue Reference Reference amino acid Variation Altered amino acid resulting from nsSNV Genomic_Variation Position of nucleotide variation within the coding frame Minor_Allele_Frequency MAF retrieved through Annovar during annotation associated with that position Source_Freq Frequency of samples containing this variant call by source PolyPhen2_Prediction Functional prediction reported by PolyPhen2 software; can be possibly damaging, probably damaging, or benign Cancer_Type Disease ontology ID (DOID) and label of cancers associated with samples containing this variant Data_Source Primary source of data from which variant calls were obtained Patient_ID Patient ID from primary source, when available PMID PubMed article ID for associated literature, when available HGMD_Disease Diseases associated with this variant in HGMD, when available HGMD_PMID PubMed article ID corresponding to publication reporting disease association in HGMD, when available TABLE S10. GOG_som_three_cancers This table contains 41 somatic variants predicted to cause a gain of the consensus NXS/T motif at that position in at least three cancer types. These variants include ONLY those somatic variants WITHOUT germline variants occurring at the same positions occurring in three or more cancers. Column name Description ================ ================================================================================== UniProtKB_AC UniProtKB/Swiss-Prot Accession Gene_name Gene name Protein_name Protein name as reported by UniProt Sequence_Length Length of protein in amino acids Signal_Peptide_Existence Describes if a signal peptide is reported for that protein in UniProt Signal_Peptide_Position Reports the annotated signal peptide position if Signal_Peptide_Existence is "Y" Cellular_component Relevant cellular component keyword(s) associated with the protein in UniProt Motif_position Position of the "N" in the identified NXS/T sequon Subsequence Four-residue sequence about the NXS/T sequon beginning with the "N" Prediction Predicted effect of variant; all should be gain_of_glycosylation Domain Domain mapping to the position, if reported Secondary_Structure Secondary structure mapping to the position, if reported Mutation_Position Position of the altered residue Reference Reference amino acid Variation Altered amino acid resulting from nsSNV Genomic_Variation Position of nucleotide variation within the coding frame Minor_Allele_Frequency MAF retrieved through Annovar during annotation associated with that position in dbSNP Source_Freq Frequency of samples containing this variant call by source PolyPhen2_Prediction Functional prediction reported by PolyPhen2 software; can be possibly damaging, probably damaging, or benign Cancer_Type Disease ontology ID (DOID) and label of cancers associated with samples containing this variant Data_Source Primary source of data from which variant calls were obtained Patient_ID Patient ID from primary source, when available PMID PubMed article ID for associated literature, when available HGMD_Disease Diseases associated with this variant in HGMD, when available HGMD_PMID PubMed article ID corresponding to publication reporting disease association in HGMD, when available NetNGlycMotif Four-residue sequence including NXS/T motif reported by NetNGlyc NetNGlycPrediction Likelihood of actual glycosylation at the sequon, as reported by NetNGlyc