Genomic Scores ============== ==================================== ======================================================================================================== Field Description ==================================== ======================================================================================================== phyloP100 Link: http://hgdownload.cse.ucsc.edu/goldenpath/hg19/phyloP100way/. Conservation scoring by phyloP (phylogenetic p-values) from the PHAST package (http://compgen.bscb.cornell.edu/phast/) for multiple alignments of 99 vertebrate genomes to the human genome. .. image:: imgs/genomic_scores/phyloP100.png :scale: 30 :alt: phyloP100 :align: center phyloP46_vertebrates Link: http://hgdownload.cse.ucsc.edu/goldenpath/hg19/phyloP46way/. Conservation scoring by phyloP (phylogenetic p-values) from the PHAST package (http://compgen.bscb.cornell.edu/phast/) for multiple alignments of 45 vertebrate genomes to the human genome, plus alternate sets of scores for the primate species and the placental mammal species in the alignments. .. image:: imgs/genomic_scores/phyloP46_vertebrates.png :scale: 30 :alt: phyloP46_vertebrates :align: center phyloP46_placentals Alternate set of phyloP46_vertebrates scores for the placental mammal subset of species in the alignments. .. image:: imgs/genomic_scores/phyloP46_placentals.png :scale: 30 :alt: phyloP46_placentals :align: center phyloP46_primates Alternate set of phyloP46_vertebrates scores for the primates subset species in the alignments. .. image:: imgs/genomic_scores/phyloP46_primates.png :scale: 30 :alt: phyloP46_primates :align: center phastCons100 Link: http://hgdownload.cse.ucsc.edu/goldenpath/hg19/phastCons100way/. Compressed phastCons scores for multiple alignments of 99 vertebrate genomes to the human genome. PhastCons is a program for identifying evolutionarily conserved elements in a multiple alignment, given a phylogenetic tree. .. image:: imgs/genomic_scores/phastCons100.png :scale: 30 :alt: phastCons100 :align: center phastCons46_vertebrates Link: http://hgdownload.cse.ucsc.edu/goldenpath/hg19/phastCons46way/. Compressed phastCons scores for multiple alignments of 45 vertebrate genomes to the human genome, plus an alternate set of scores for the primates subset of species in the alignments, and an alternate set of scores for the placental mammal subset of species in the alignments. PhastCons is a program for identifying evolutionarily conserved elements in a multiple alignment, given a phylogenetic tree. .. image:: imgs/genomic_scores/phastCons46_vertebrates.png :scale: 30 :alt: phastCons46_vertebrates :align: center phastCons46_placentals Alternate set of phastCons46_vertebrates scores for the placental mammal subset of species in the alignments. .. image:: imgs/genomic_scores/phastCons46_placentals.png :scale: 30 :alt: phastCons46_placentals :align: center phastCons46_primates Alternate set of phastCons46_vertebrates scores for the primates subset of species in the alignments. .. image:: imgs/genomic_scores/phastCons46_primates.png :scale: 30 :alt: phastCons46_primates :align: center CADD_raw Link: https://cadd.gs.washington.edu/download ; Higher values of raw scores have relative meaning that a variant is more likely to be simulated (or "not observed") and therefore more likely to have deleterious effects. Scaled scores are PHRED-like (-10*log10(rank/total)) scaled C-score ranking a variant relative to all possible substitutions of the human genome (8.6x10^9). .. image:: imgs/genomic_scores/CADD_raw_gs.png :scale: 30 :alt: CADD raw :align: center CADD_phred Link: https://cadd.gs.washington.edu/download ; Higher values of raw scores have relative meaning that a variant is more likely to be simulated (or "not observed") and therefore more likely to have deleterious effects. Scaled scores are PHRED-like (-10*log10(rank/total)) scaled C-score ranking a variant relative to all possible substitutions of the human genome (8.6x10^9). .. image:: imgs/genomic_scores/CADD_phred_gs.png :scale: 30 :alt: CADD phred :align: center Linsight Linsight scores for prediction of deleterious noncoding variants .. image:: imgs/genomic_scores/Linsight.png :scale: 30 :alt: Linsight :align: center FitCons i6 merged Link: http://compgen.cshl.edu/fitCons/0downloads/tracks/i6/scores/. Indicates the fraction of genomic positions evincing a particular pattern (or "fingerprint") of functional assay results, that are under selective pressure. Score ranges from 0.0 to 1.0. A lower score indicates higher confidence. .. image:: imgs/genomic_scores/FitCons-i6-merged.png :scale: 30 :alt: FitCons-i6-merged :align: center Brain Angular Gyrus FitCons2 Scores for E067-Brain Angular Gyrus score-Roadmap Epigenomics DHS regions .. image:: imgs/genomic_scores/FitCons2_E067.png :scale: 30 :alt: FitCons2 E067-Brain Angular Gyrus :align: center Brain Anterior Caudate Scores for E068-Brain Anterior Caudate score-Roadmap Epigenomics DHS regions .. figure:: imgs/genomic_scores/FitCons2_E068.png :scale: 50 :alt: FitCons2 E068-Brain Anterior Caudate :align: center Brain Cingulate Gyrus Scores for E069-Brain Cingulate Gyrus score-Roadmap Epigenomics DHS regions .. figure:: imgs/genomic_scores/FitCons2_E069.png :scale: 50 :alt: FitCons2 E069-Brain Cingulate Gyrus :align: center Brain Germinal Matrix Scores for E070-Brain Germinal Matrix score-Roadmap Epigenomics DHS regions .. figure:: imgs/genomic_scores/FitCons2_E070.png :scale: 50 :alt: FitCons2 E070-Brain Germinal Matrix :align: center Brain Hippocampus Middle Scores for E071-Brain Hippocampus Middle score-Roadmap Epigenomics DHS regions .. figure:: imgs/genomic_scores/FitCons2_E071.png :scale: 50 :alt: FitCons2 E071-Brain Hippocampus Middle :align: center Brain Inferior Temporal Lobe Scores for E072-Brain Inferior Temporal Lobe score-Roadmap Epigenomics DHS regions .. figure:: imgs/genomic_scores/FitCons2_E072.png :scale: 50 :alt: FitCons2 E072-Brain Inferior Temporal Lobe :align: center Brain Dorsolateral Prefrontal Cortex Scores for E073-Brain Dorsolateral Prefrontal Cortex score-Roadmap Epigenomics DHS regions .. figure:: imgs/genomic_scores/FitCons2_E073.png :scale: 50 :alt: FitCons2 E073-Brain Dorsolateral Prefrontal Cortex :align: center Brain Substantia Nigra Scores for E074-Brain Substantia Nigra score-Roadmap Epigenomics DHS regions .. figure:: imgs/genomic_scores/FitCons2_E074.png :scale: 50 :alt: FitCons2 E074-Brain Substantia Nigra :align: center Fetal Brain Male Scores for E081-Fetal Brain Male score-Roadmap Epigenomics DHS regions .. figure:: imgs/genomic_scores/FitCons2_E081.png :scale: 50 :alt: FitCons2 E081-Fetal Brain Male :align: center Fetal Brain Female Scores for E082-Fetal Brain Female score-Roadmap Epigenomics DHS regions .. figure:: imgs/genomic_scores/FitCons2_E082.png :scale: 50 :alt: FitCons2 E082-Fetal Brain Female :align: center SSC Frequency SSC Frequency .. figure:: imgs/genomic_scores/SSC-freq.png :scale: 50 :alt: SSC Frequency :align: center genome gnomAD AC Allele counts for the genome-only subset of gnomAD v2.1. genome gnomAD AN Allele numbers for the genome-only subset of gnomAD v2.1. genome gnomAD AF Allele frequencies for the genome-only subset of gnomAD v2.1. gnomAD v2.1 comprises a total of 16mln SNVs and 1.2mln indels from 125,748 exomes, and 229mln SNVs and 33mln indels from 15,708 genomes. (Cited from https://macarthurlab.org/2018/10/17/gnomad-v2-1/) *"The raw counts (ac and an) refer to the total number of chromosomes with this allele, and total that were able to be called (whether reference or alternate), respectively. Thus, the allele frequency is ac/an."* (Cited from https://macarthurlab.org/2016/03/17/reproduce-all-the-figures-a-users-guide-to-exac-part-2/) *"Deleterious variants are expected to have lower allele frequencies than neutral ones, due to negative selection."* (Cited from the ExAC paper, p.10, 'Inferring variant deleteriousness and gene constraint') A total of 15,708 genomes. (Cited from https://gnomad.broadinstitute.org/faq) .. figure:: imgs/genomic_scores/genome_gnomAD-AF.png :scale: 50 :alt: genome gnomAD allele frequency :align: center genome gnomAD AF percent Allele frequencies for the genome-only subset of gnomAD v2.1, as a percentage. (i.e. multiplied by 100.0) .. figure:: imgs/genomic_scores/genome_gnomAD-AF_percent.png :scale: 50 :alt: genome gnomAD allele frequency percent :align: center genome gnomAD controls AC Controls-only allele counts for the genome-only subset of gnomAD v2.1. (Only samples from individuals who were not selected as a case in a case/control study of common disease.) genome gnomAD controls AN Controls-only allele numbers for the genome-only subset of gnomAD v2.1. (Only samples from individuals who were not selected as a case in a case/control study of common disease.) genome gnomAD controls AF Controls-only allele frequencies for the genome-only subset of gnomAD v2.1. (Only samples from individuals who were not selected as a case in a case/control study of common disease.) .. figure:: imgs/genomic_scores/genome_gnomAD-controls_AF.png :scale: 50 :alt: controls genome gnomAD allele frequency :align: center genome gnomAD controls AF percent Controls-only allele frequencies for the genome-only subset of gnomAD v2.1, as a percentage. (i.e. multiplied by 100.0) (Only samples from individuals who were not selected as a case in a case/control study of common disease.) .. figure:: imgs/genomic_scores/genome_gnomAD-controls_AF_percent.png :scale: 50 :alt: controls genome gnomAD allele frequency percent :align: center genome gnomAD non-neuro AC Non-neuro allele counts for the genome-only subset of gnomAD v2.1. (Only samples from individuals who were not ascertained for having a neurological condition in a neurological case/control study) genome gnomAD non-neuro AN Non-neuro allele numbers for the genome-only subset of gnomAD v2.1. (Only samples from individuals who were not ascertained for having a neurological condition in a neurological case/control study) genome gnomAD non-neuro AF Non-neuro allele frequencies for the genome-only subset of gnomAD v2.1. (Only samples from individuals who were not ascertained for having a neurological condition in a neurological case/control study) .. figure:: imgs/genomic_scores/genome_gnomAD-non_neuro_AF.png :scale: 50 :alt: non-neuro genome gnomAD allele frequency :align: center genome gnomAD non-neuro AF percent Non-neuro allele frequencies for the genome-only subset of gnomAD v2.1, as a percentage. (i.e. multiplied by 100.0) (Only samples from individuals who were not ascertained for having a neurological condition in a neurological case/control study) .. figure:: imgs/genomic_scores/genome_gnomAD-non_neuro_AF_percent.png :scale: 50 :alt: non-neuro genome gnomAD allele frequency percent :align: center exome gnomAD AC Allele counts for the exome-only subset of gnomAD v2.1. exome gnomAD AN Allele numbers for the exome-only subset of gnomAD v2.1. exome gnomAD AF Allele frequencies for the exome-only subset of gnomAD v2.1. A total of 125,748 exomes. (Cited from https://gnomad.broadinstitute.org/faq) .. figure:: imgs/genomic_scores/exome_gnomAD-AF.png :scale: 50 :alt: exome gnomAD allele frequency :align: center exome gnomAD AF percent Allele frequencies for the exome-only subset of gnomAD v2.1, as a percentage. (i.e. multiplied by 100.0) .. figure:: imgs/genomic_scores/exome_gnomAD-AF_percent.png :scale: 50 :alt: exome gnomAD allele frequency percent :align: center exome gnomAD controls AC Controls-only allele counts for the exome-only subset of gnomAD v2.1. (Only samples from individuals who were not selected as a case in a case/control study of common disease.) exome gnomAD controls AN Controls-only allele numbers for the exome-only subset of gnomAD v2.1. (Only samples from individuals who were not selected as a case in a case/control study of common disease.) exome gnomAD controls AF Controls-only allele frequencies for the exome-only subset of gnomAD v2.1. (Only samples from individuals who were not selected as a case in a case/control study of common disease.) .. figure:: imgs/genomic_scores/exome_gnomAD-controls_AF.png :scale: 50 :alt: controls exome gnomAD allele frequency :align: center exome gnomAD controls AF percent Controls-only allele frequencies for the exome-only subset of gnomAD v2.1, as a percentage. (i.e. multiplied by 100.0) (Only samples from individuals who were not selected as a case in a case/control study of common disease.) .. figure:: imgs/genomic_scores/exome_gnomAD-controls_AF_percent.png :scale: 50 :alt: controls exome gnomAD allele frequency percent :align: center exome gnomAD non-neuro AC Non-neuro allele counts for the exome-only subset of gnomAD v2.1. (Only samples from individuals who were not ascertained for having a neurological condition in a neurological case/control study) exome gnomAD non-neuro AN Non-neuro allele numbers for the exome-only subset of gnomAD v2.1. (Only samples from individuals who were not ascertained for having a neurological condition in a neurological case/control study) exome gnomAD non-neuro AF Non-neuro allele frequencies for the exome-only subset of gnomAD v2.1. (Only samples from individuals who were not ascertained for having a neurological condition in a neurological case/control study) .. figure:: imgs/genomic_scores/exome_gnomAD-non_neuro_AF.png :scale: 50 :alt: non-neuro exome gnomAD allele frequency :align: center exome gnomAD non-neuro AF percent Non-neuro allele frequencies for the exome-only subset of gnomAD v2.1, as a percentage. (i.e. multiplied by 100.0) (Only samples from individuals who were not ascertained for having a neurological condition in a neurological case/control study) .. figure:: imgs/genomic_scores/exome_gnomAD-non_neuro_AF_percent.png :scale: 50 :alt: non-neuro exome gnomAD allele frequency percent :align: center MPC MPC - Missense badness, PolyPhen-2, and Constraint - `MPC paper`_ - `MPC paper supplement`_ Downloaded from: `MPC download link`_ .. figure:: imgs/genomic_scores/MPC.png :scale: 50 :alt: MPC :align: center ==================================== ======================================================================================================== .. _`MPC download link`: ftp://ftp.broadinstitute.org/pub/ExAC_release/release1/regional_missense_constraint/fordist_constraint_official_mpc_values_v2.txt.gz .. _`MPC paper`: https://www.biorxiv.org/content/biorxiv/early/2017/06/12/148353.full.pdf .. _`MPC paper supplement`: https://www.biorxiv.org/content/biorxiv/suppl/2017/06/12/148353.DC1/148353-1.pdf