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0000000000000000000000000000000000000000..0b1bac9985163a663aef4d55d687d9ddd945f51f --- /dev/null +++ b/3D/GSE63525_GM12878_combined_README.rtf @@ -0,0 +1,174 @@ +{\rtf1\ansi\ansicpg1252\cocoartf1265\cocoasubrtf210 +{\fonttbl\f0\fswiss\fcharset0 Helvetica;\f1\fnil\fcharset0 Menlo-Regular;} +{\colortbl;\red255\green255\blue255;} +\margl1440\margr1440\vieww28600\viewh16520\viewkind0 +\pard\tx720\tx1440\tx2160\tx2880\tx3600\tx4320\tx5040\tx5760\tx6480\tx7200\tx7920\tx8640\pardirnatural + +\f0\fs24 \cf0 READ ME:\ +\ +The archive \'91GM12878_combined_contact_matrices.tar.gz\'92 contains the raw observed contact matrices for the GM12878 combined (primary+replicate) map presented in Rao, Huntley, et al, Cell, 2014 as well as normalization vectors to transform the raw matrices into normalized matrices and 1-d expected vectors to transform the observed matrices into O/E matrices (see the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014 for details). \ +\ +Data from the following experiments is contained in the GM12878 combined contact matrices:\ +HIC001\ +HIC002\ +HIC003\ +HIC004\ +HIC005\ +HIC006\ +HIC007\ +HIC008\ +HIC009\ +HIC010\ +HIC011\ +HIC012\ +HIC013\ +HIC014\ +HIC015\ +HIC016\ +HIC017\ +HIC018\ +HIC019\ +HIC020\ +HIC021\ +HIC022\ +HIC023\ +HIC024\ +HIC025\ +HIC026\ +HIC027\ +HIC028\ +HIC029\ +\ +See Supplemental Table S1 of Rao, Huntley, et al, Cell, 2014 for more details regarding the individual experiments.\ +\ +The archive contains intrachromosomal contact matrices at 10 different base pair delimited resolutions (1 Mb, 500kb, 250kb, 100kb, 50kb, 25kb, 10kb, 5kb, 1kb). At each resolution, files associated with each chromosome are provided in a separate subdirectory. Within, each chromosome subdirectory, there are two further subdirectories (MAPQG0 and MAPQGE30). The MAPQG0 subdirectory contains files associated with the contact matrices constructed from all read pairs that uniquely align to the genome (MAPQ>0). The MAPQGE30 subdirectory contains files associated with the contact matrices constructed from all read pairs that map to the genome with a MAPQ>=30. \ +\ +For example, the files associated with the contact matrix for chromosome 1 at 5 kb resolution using MAPQ>=30 read pairs are in the subdirectory:\ +\ +GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/\ +\ +There are 7 text files associated with each intrachromosomal contact matrix ([CHR] represents the chromosome number and [RES] represents the resolution):\ +\ +[CHR]_[RES].RAWobserved\ +[CHR]_[RES].KRnorm\ +[CHR]_[RES].VCnorm\ +[CHR]_[RES].SQRTVCnorm\ +[CHR]_[RES].RAWexpected\ +[CHR]_[RES].KRexpected\ +[CHR]_[RES].VCexpected\ +[CHR]_[RES].SQRTVCexpected\ +\ +For example, the files associated with the contact matrix for chromosome 1 at 5 kb resolution using MAPQ>=30 read pairs are:\ +\ +GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.RAWobserved\ +GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.KRnorm\ +GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.VCnorm\ +GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.SQRTVCnorm\ +GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.RAWexpected\ +GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.KRexpected\ +GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.VCexpected\ +GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.SQRTVCexpected\ +\ +*.RAWobserved is a text file with the raw observed contact matrix in sparse matrix notation. Each line has three fields: i, j, and M_i,j. (i and j are written as the left edge of the bin at a given resolution; for example, at 100 kb resolution, the entry corresponding to the first row and tenth column of the matrix would correspond to M_i,j, where i=0, j=900000). Only the upper triangle of the matrix is provided (i.e. i>=j), the matrix is symmetric, so M_i,j = M_j,i. \ +\ +The three *norm files are normalization vectors that can be used to transform the raw contact matrices M into normalized matrices M*. (See the glossary below and section II.b of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014 for more information about the different types of normalizations. All analyses and results presented in the main text of Rao, Huntley, et al, Cell, 2014 were performed using KR normalized contact matrices.) Each file is ordered such that the first line of the normalization vector file is the norm factor for the first row/column of the corresponding raw contact matrix, the second line is the factor for the second row/column of the contact matrix, and so on. To normalize, an entry M_i,j in a *RAWobserved file, divide the entry by the corresponding norm factors for i and j. \ +\ +For example, here is a line from the 5kb chr1 MAPQGE30 raw observed contact matrix (GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.RAWobserved):\ +\pard\tx560\tx1120\tx1680\tx2240\tx2800\tx3360\tx3920\tx4480\tx5040\tx5600\tx6160\tx6720\pardirnatural + +\f1\fs22 \cf0 \CocoaLigature0 40000000 40100000 59.0\ +\ +\pard\tx720\tx1440\tx2160\tx2880\tx3600\tx4320\tx5040\tx5760\tx6480\tx7200\tx7920\tx8640\pardirnatural + +\f0\fs24 \cf0 \CocoaLigature1 To normalize this entry using the KR normalization vector, one would divide 59.0 by the 8001st line ((40000000/5000)+1=8001) and the 8021st line ((40100000/5000)+1=8021) of GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.KRnorm. The 8001st line of the KR norm file is +\f1\fs22 \CocoaLigature0 1.2988778370674694; +\f0\fs24 \CocoaLigature1 The 8021st line of the KR norm file is +\f1\fs22 \CocoaLigature0 1.6080499717941548. +\f0\fs24 \CocoaLigature1 So the corresponding KR normalized entry for the entry above is +\f1\fs22 \CocoaLigature0 59.0/(1.2988778370674694*1.6080499717941548) +\f0\fs24 \CocoaLigature1 or +\f1\fs22 \CocoaLigature0 28.24776973966101. +\f0\fs24 \CocoaLigature1 If the KR normalization vector file is empty or all NaNs, then the KR algorithm didn\'92t converge on that particular matrix (likely due to sparsity of the matrix). +\f1\fs22 \CocoaLigature0 \ +\ + +\f0\fs24 \CocoaLigature1 The four *expected files are expected vectors that can be used to construct O/E matrices that account for the increased number of contacts seen at short distances due to to random polymer interactions driven by one-dimensional genome proximity (see the glossary below and section II.c of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014 for more information about the construction of these expected vectors and O/E matrices). These expected files are ordered such that first line of the expected vector file is the expected number of contacts between two loci separated by 0*RES base pairs, the second line of the file is the expected number of contacts between two loci separated by 1*RES base pairs, and so on. So to create the O/E matrix, divide each entry M_i,j by the expected value corresponding to the distance i-j. \ +\ +For example, for the above entry of the 5kb chr1 MAPQGE30 raw observed contact matrix, to get the corresponding entry of the O/E matrix divide by the 21st line (((41000000-40000000)/5000)+1=21) of GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.RAWexpected. The 21st line of the raw expected file is +\f1\fs22 \CocoaLigature0 20.101675. +\f0\fs24 \CocoaLigature1 So the corresponding raw O/E entry for the entry above is +\f1\fs22 \CocoaLigature0 59.0/20.101675 or 2.935078793185145. +\f0\fs24 \CocoaLigature1 To create the normalized O/E files, first construct the normalized observed matrices as above and then divide by the corresponding line of the normalized expected file (i.e. *.KRexpected, *.VCexpected, or *.SQRTVCexpected). \ +\ +The archive also contains interchromosomal contact matrices at 100kb resolution. The files associated with each pair of chromosomes are provided in a separated subdirectory. Within each chromosome pair subdirectory, there are two further subdirectories (MAPQG0 and MAPQGE30). The MAPQG0 subdirectory contains files associated with the contact matrices constructed from all read pairs that uniquely align to the genome (MAPQ>0). The MAPQGE30 subdirectory contains files associated with the contact matrices constructed from all read pairs that map to the genome with a MAPQ>=30.\ +\ +For example, the files associated with the contact matrix for chromosome 1 and chromosome 2 using MAPQ>=30 read pairs are in the subdirectory:\ +\ +GM12878_combined/100kb_resolution_interchromosomal/chr1_chr2/MAPQGE30/\ +\ +There are 15 text files associated with each interchromosomal contact matrix ([CHR1] represents the first chromosome number, [CHR2] represents the second chromosome number, and [RES] represents the resolution):\ +\ +[CHR1]_[CHR2]_[RES].RAWobserved\ +[CHR1]_[RES].KRnorm\ +[CHR1]_[RES].VCnorm\ +[CHR1]_[RES].SQRTVCnorm +\f1\fs22 \CocoaLigature0 \ + +\f0\fs24 \CocoaLigature1 [CHR1]_[RES].INTERKRnorm +\f1\fs22 \CocoaLigature0 \ + +\f0\fs24 \CocoaLigature1 [CHR1]_[RES].INTERVCnorm\ +[CHR1]_[RES].GWKRnorm\ +[CHR1]_[RES].GWVCnorm\ +[CHR2]_[RES].KRnorm\ +[CHR2]_[RES].VCnorm\ +[CHR2]_[RES].SQRTVCnorm +\f1\fs22 \CocoaLigature0 \ + +\f0\fs24 \CocoaLigature1 [CHR2]_[RES].INTERKRnorm +\f1\fs22 \CocoaLigature0 \ + +\f0\fs24 \CocoaLigature1 [CHR2]_[RES].INTERVCnorm\ +[CHR2]_[RES].GWKRnorm\ +[CHR2]_[RES].GWVCnorm\ +\ +For example, the files associated with the contact matrix for chromosome 1 and chromosome 2 using MAPQ>=30 read pairs are:\ +\ +chr1_2_100kb.RAWobserved\ +chr1_100kb.KRnorm\ +chr1_100kb.VCnorm\ +chr1_100kb.SQRTVCnorm +\f1\fs22 \CocoaLigature0 \ + +\f0\fs24 \CocoaLigature1 chr1_100kb.INTERKRnorm +\f1\fs22 \CocoaLigature0 \ + +\f0\fs24 \CocoaLigature1 chr1_100kb.INTERVCnorm\ +chr1_100kb.GWKRnorm\ +chr1_100kb.GWVCnorm\ +chr2_100kb.KRnorm\ +chr2_100kb.VCnorm\ +chr2_100kb.SQRTVCnorm +\f1\fs22 \CocoaLigature0 \ + +\f0\fs24 \CocoaLigature1 chr2_100kb.INTERKRnorm +\f1\fs22 \CocoaLigature0 \ + +\f0\fs24 \CocoaLigature1 chr2_100kb.INTERVCnorm\ +chr2_100kb.GWKRnorm\ +chr2_100kb.GWVCnorm\ +\ +The *.RAWobserved files for the interchromosomal matrices are formatted the same way as the intrachromosomal matrices above except the i locus corresponds to CHR1 and the j locus corresponds to CHR2. One can create the normalized matrices as above except one should use the line corresponding to the i locus norm factor from the CHR1 normalization vector file and the line corresponding to the j locus norm factor from the CHR2 normalization vector file. (See the glossary below and section II.b of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014 for more information about the different types of normalizations.)\ +\ +GLOSSARY:\ +KRnorm = normalization vector obtained using the matrix balancing procedure of Knight and Ruiz on the intrachromosomal contact matrix, as reimplemented by us in Java. See Knight & Ruiz, IMA Journal of Numerical Analysis, 2012; section II.b.4 of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014.\ +GWKRnorm = normalization vector obtained using the matrix balancing procedure of Knight and Ruiz on the entire genome-wide contact matrix (i.e. all intrachromosomal and interchromosomal contact matrices), as reimplemented by us in Java. See Knight & Ruiz, IMA Journal of Numerical Analysis, 2012; section II.b.4 of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014.\ +INTERKRnorm = normalization vector obtained using the matrix balancing procedure of Knight and Ruiz on the entire genome-wide contact matrix without intrachromosomal contact matrices (i.e. only interchromosomal contact matrices), as reimplemented by us in Java. See Knight & Ruiz, IMA Journal of Numerical Analysis, 2012; section II.b.4 of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014.\ +VCnorm = normalization vector obtained by calculating coverages (row-sums of the intrachromosomal contact matrix) for each locus as performed in Lieberman-Aiden, van Berkum, et al. See Lieberman-Aiden, van Berkum, et al, Science 2009; section II.b.1 of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014.\ +GWVCnorm = normalization vector obtained by calculating genome-wide coverages (row-sums of the genome-wide contact matrix, i.e. both intra- and inter-chromosomal contact matrices) for each locus as performed in Lieberman-Aiden, van Berkum, et al. See Lieberman-Aiden, van Berkum, et al, Science 2009; section II.b.1 of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014.\ +INTERVCnorm = normalization vector obtained by calculating interchromosomal coverages (row-sums across interchromosomal contact matrices) for each locus as performed in Lieberman-Aiden, van Berkum, et al. See Lieberman-Aiden, van Berkum, et al, Science 2009; section II.b.1 of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014.\ +SQRTVCnorm = normalization vector obtained by taking the square root of the VCnorm vector. See section II.b.1 of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014.\ +RAWexpected = a genome-wide model of interaction probability as a function of 1-dimensional genomic distance as introduced in Lieberman-Aiden, van Berkum, et al. and refined by us. See Lieberman-Aiden, van Berkum, et al, Science 2009; section II.c.1 of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014.\ +KRexpected = the same model of interaction probability as a function of 1-dimensional genomic distance as RAWexpected except calculated from the KR normalized contact matrix. \ +VCexpected = the same model of interaction probability as a function of 1-dimensional genomic distance as RAWexpected except calculated from the VC normalized contact matrix. \ +SQRTVCexpected = the same model of interaction probability as a function of 1-dimensional genomic distance as RAWexpected except calculated from the SQRTVC normalized contact matrix.} diff --git a/3D/GSE63525_K562_README.rtf b/3D/GSE63525_K562_README.rtf new file mode 100644 index 0000000000000000000000000000000000000000..11f78e313c2acde584a3a188b0b25488d8a82207 --- /dev/null +++ b/3D/GSE63525_K562_README.rtf @@ -0,0 +1,88 @@ +{\rtf1\ansi\ansicpg1252\cocoartf1265\cocoasubrtf210 +{\fonttbl\f0\fswiss\fcharset0 Helvetica;\f1\fnil\fcharset0 Menlo-Regular;} +{\colortbl;\red255\green255\blue255;} +\margl1440\margr1440\vieww28600\viewh16520\viewkind0 +\pard\tx720\tx1440\tx2160\tx2880\tx3600\tx4320\tx5040\tx5760\tx6480\tx7200\tx7920\tx8640\pardirnatural + +\f0\fs24 \cf0 READ ME:\ +\ +The archive \'91K562_contact_matrices.tar.gz\'92 contains the raw observed contact matrices for the K562 map presented in Rao, Huntley, et al, Cell, 2014 as well as normalization vectors to transform the raw matrices into normalized matrices and 1-d expected vectors to transform the observed matrices into O/E matrices (see the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014 for details). \ +\ +Data from the following experiments is contained in the K562 contact matrices:\ +HIC069\ +HIC070\ +HIC071\ +HIC072\ +HIC073\ +HIC074\ +\ +See Supplemental Table S1 of Rao, Huntley, et al, Cell, 2014 for more details regarding the individual experiments.\ +\ +The archive contains intrachromosomal contact matrices at 9 different base pair delimited resolutions (1 Mb, 500kb, 250kb, 100kb, 50kb, 25kb, 10kb, 5kb). At each resolution, files associated with each chromosome are provided in a separate subdirectory. Within, each chromosome subdirectory, there are two further subdirectories (MAPQG0 and MAPQGE30). The MAPQG0 subdirectory contains files associated with the contact matrices constructed from all read pairs that uniquely align to the genome (MAPQ>0). The MAPQGE30 subdirectory contains files associated with the contact matrices constructed from all read pairs that map to the genome with a MAPQ>=30. \ +\ +For example, the files associated with the contact matrix for chromosome 1 at 5 kb resolution using MAPQ>=30 read pairs are in the subdirectory:\ +\ +K562/5kb_resolution_intrachromosomal/chr1/MAPQGE30/\ +\ +There are 7 text files associated with each intrachromosomal contact matrix ([CHR] represents the chromosome number and [RES] represents the resolution):\ +\ +[CHR]_[RES].RAWobserved\ +[CHR]_[RES].KRnorm\ +[CHR]_[RES].VCnorm\ +[CHR]_[RES].SQRTVCnorm\ +[CHR]_[RES].RAWexpected\ +[CHR]_[RES].KRexpected\ +[CHR]_[RES].VCexpected\ +[CHR]_[RES].SQRTVCexpected\ +\ +For example, the files associated with the contact matrix for chromosome 1 at 5 kb resolution using MAPQ>=30 read pairs are:\ +\ +K562/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.RAWobserved\ +K562/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.KRnorm\ +K562/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.VCnorm\ +K562/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.SQRTVCnorm\ +K562/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.RAWexpected\ +K562/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.KRexpected\ +K562/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.VCexpected\ +K562/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.SQRTVCexpected\ +\ +*.RAWobserved is a text file with the raw observed contact matrix in sparse matrix notation. Each line has three fields: i, j, and M_i,j. (i and j are written as the left edge of the bin at a given resolution; for example, at 100 kb resolution, the entry corresponding to the first row and tenth column of the matrix would correspond to M_i,j, where i=0, j=900000). Only the upper triangle of the matrix is provided (i.e. i>=j), the matrix is symmetric, so M_i,j = M_j,i. \ +\ +The three *norm files are normalization vectors that can be used to transform the raw contact matrices M into normalized matrices M*. (See the glossary below and section II.b of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014 for more information about the different types of normalizations. All analyses and results presented in the main text of Rao, Huntley, et al, Cell, 2014 were performed using KR normalized contact matrices.) Each file is ordered such that the first line of the normalization vector file is the norm factor for the first row/column of the corresponding raw contact matrix, the second line is the factor for the second row/column of the contact matrix, and so on. To normalize, an entry M_i,j in a *RAWobserved file, divide the entry by the corresponding norm factors for i and j. \ +\ +For example, here is a line from the 5kb chr1 MAPQGE30 raw observed contact matrix (K562/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.RAWobserved):\ +\pard\tx560\tx1120\tx1680\tx2240\tx2800\tx3360\tx3920\tx4480\tx5040\tx5600\tx6160\tx6720\pardirnatural + +\f1\fs22 \cf0 \CocoaLigature0 40000000 40100000 13.0\ +\ +\pard\tx720\tx1440\tx2160\tx2880\tx3600\tx4320\tx5040\tx5760\tx6480\tx7200\tx7920\tx8640\pardirnatural + +\f0\fs24 \cf0 \CocoaLigature1 To normalize this entry using the KR normalization vector, one would divide 59.0 by the 8001st line ((40000000/5000)+1=8001) and the 8021st line ((40100000/5000)+1=8021) of K562/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.KRnorm. The 8001st line of the KR norm file is +\f1\fs22 \CocoaLigature0 1.391205327929388; +\f0\fs24 \CocoaLigature1 The 8021st line of the KR norm file is +\f1\fs22 \CocoaLigature0 1.764507526190848. +\f0\fs24 \CocoaLigature1 So the corresponding KR normalized entry for the entry above is +\f1\fs22 \CocoaLigature0 13.0/(1.391205327929388*1.764507526190848) +\f0\fs24 \CocoaLigature1 or +\f1\fs22 \CocoaLigature0 5.2957637802416944. +\f0\fs24 \CocoaLigature1 If the KR normalization vector file is empty or all NaNs, then the KR algorithm didn\'92t converge on that particular matrix (likely due to sparsity of the matrix). +\f1\fs22 \CocoaLigature0 \ +\ + +\f0\fs24 \CocoaLigature1 The four *expected files are expected vectors that can be used to construct O/E matrices that account for the increased number of contacts seen at short distances due to to random polymer interactions driven by one-dimensional genome proximity (see the glossary below and section II.c of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014 for more information about the construction of these expected vectors and O/E matrices). These expected files are ordered such that first line of the expected vector file is the expected number of contacts between two loci separated by 0*RES base pairs, the second line of the file is the expected number of contacts between two loci separated by 1*RES base pairs, and so on. So to create the O/E matrix, divide each entry M_i,j by the expected value corresponding to the distance i-j. \ +\ +For example, for the above entry of the 5kb chr1 MAPQGE30 raw observed contact matrix, to get the corresponding entry of the O/E matrix divide by the 21st line (((41000000-40000000)/5000)+1=21) of K562/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.RAWexpected. The 21st line of the raw expected file is +\f1\fs22 \CocoaLigature0 5.357775. +\f0\fs24 \CocoaLigature1 So the corresponding raw O/E entry for the entry above is +\f1\fs22 \CocoaLigature0 13.0/5.357775 or 2.42638035378492. +\f0\fs24 \CocoaLigature1 To create the normalized O/E files, first construct the normalized observed matrices as above and then divide by the corresponding line of the normalized expected file (i.e. *.KRexpected, *.VCexpected, or *.SQRTVCexpected). \ +\ +GLOSSARY:\ +KRnorm = normalization vector obtained using the matrix balancing procedure of Knight and Ruiz on the intrachromosomal contact matrix, as reimplemented by us in Java. See Knight & Ruiz, IMA Journal of Numerical Analysis, 2012; section II.b.4 of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014.\ +VCnorm = normalization vector obtained by calculating coverages (row-sums of the intrachromosomal contact matrix) for each locus as performed in Lieberman-Aiden, van Berkum, et al. See Lieberman-Aiden, van Berkum, et al, Science 2009; section II.b.1 of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014.\ +SQRTVCnorm = normalization vector obtained by taking the square root of the VCnorm vector. See section II.b.1 of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014.\ +RAWexpected = a genome-wide model of interaction probability as a function of 1-dimensional genomic distance as introduced in Lieberman-Aiden, van Berkum, et al. and refined by us. See Lieberman-Aiden, van Berkum, et al, Science 2009; section II.c.1 of the Extended Experimental Procedures of Rao, Huntley, et al, Cell, 2014.\ +KRexpected = the same model of interaction probability as a function of 1-dimensional genomic distance as RAWexpected except calculated from the KR normalized contact matrix. \ +VCexpected = the same model of interaction probability as a function of 1-dimensional genomic distance as RAWexpected except calculated from the VC normalized contact matrix. \ +SQRTVCexpected = the same model of interaction probability as a function of 1-dimensional genomic distance as RAWexpected except calculated from the SQRTVC normalized contact matrix.\ +} diff --git a/3D/GSE63525_OVERALL_README.rtf b/3D/GSE63525_OVERALL_README.rtf new file mode 100644 index 0000000000000000000000000000000000000000..e1fed635adccdd83879a80b3e19331b8aed41c63 --- /dev/null +++ b/3D/GSE63525_OVERALL_README.rtf @@ -0,0 +1,605 @@ 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{\pntxta )}}{\*\pnseclvl5\pndec\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}{\*\pnseclvl6 +\pnlcltr\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}{\*\pnseclvl7\pnlcrm\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}{\*\pnseclvl8\pnlcltr\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}{\*\pnseclvl9\pnlcrm\pnstart1\pnindent720\pnhang +{\pntxtb (}{\pntxta )}}\pard\plain \ltrpar\ql \li0\ri0\nowidctlpar\tx720\tx1440\tx2160\tx2880\tx3600\tx4320\tx5040\tx5760\tx6480\tx7200\tx7920\tx8640\wrapdefault\faauto\rin0\lin0\itap0 \rtlch\fcs1 \af31507\afs22\alang1025 \ltrch\fcs0 +\fs22\lang1033\langfe1033\loch\af31506\hich\af31506\dbch\af31505\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \ab\af4\afs24 \ltrch\fcs0 \b\f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 README:}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 \hich\f4 This README describes the various files and file formats that have been uploaded to GEO accession GSE63525 as part of the study \'93\loch\f4 \hich\f4 +A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping\'94\hich\af4\dbch\af31505\loch\f4 (Rao and Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{ +\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid4858580 \hich\af4\dbch\af31505\loch\f4 , Cell 2014).}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 As part of this study, we have uploaded data at various processing stages, including: +\par \hich\af4\dbch\af31505\loch\f4 - raw sequence data (FASTQ format) +\par \hich\af4\dbch\af31505\loch\f4 - data post-alignment and duplicate filtering (merged_nodups.txt format) +\par \hich\af4\dbch\af31505\loch\f4 - contact matrices and\hich\af4\dbch\af31505\loch\f4 associated normalization and 1-D expected vectors (tar archives) +\par \hich\af4\dbch\af31505\loch\f4 - feature annotations (loop annotations, contact domain annotations, subcompartment annotation for GM12878, super loop annotation for GM12878, intersect SNP list for GM12878) +\par +\par \hich\af4\dbch\af31505\loch\f4 The various fi\hich\af4\dbch\af31505\loch\f4 les and file formats associated with each processing stage will be described in more detail below. +\par +\par }{\rtlch\fcs1 \ab\ai\af4\afs24 \ltrch\fcs0 \b\i\f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 Raw Data:}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 FASTQ data for all the experiments performed in this study are available through SRA under the Sample Record for each experiment. Each experiment\hich\af4\dbch\af31505\loch\f4 \hich\f4 is labeled with a unique identifier: +\'93\loch\f4 \hich\f4 HIC\'94\loch\f4 followed by a three digit number (for example, HIC001 or HIC100). Full details for each experiment (including, but not limited to: cell type, experimental variations, number of reads sequenced, etc.) as well as +\hich\af4\dbch\af31505\loch\f4 w\hich\af4\dbch\af31505\loch\f4 hich experiments were combined together to create the high resolution maps for each cell type are available in Supplemental Table S1 of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell, 2014. Some information about each experiment (such as cell type and a general description of +\hich\af4\dbch\af31505\loch\f4 the experimental protocol used) is also available in each individual sample record. +\par +\par }{\rtlch\fcs1 \ab\ai\af4\afs24 \ltrch\fcs0 \b\i\f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 Post-alignment and Duplicate Filtering Data:}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 Under each Sample Record, there is a file available named GSM*_HIC*_merged_nodups.txt.gz, where GSM* is the GEO Sample ID and\hich\af4\dbch\af31505\loch\f4 + HIC* is the unique sample identifier from Supplemental Table S1 of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\hich\af4\dbch\af31505\loch\f4 , Cell, 2014. This file contains post-alignment and post-duplicate filtering data for each HIC experiment. At this stage of processing, read pairs where one or both ends\hich\af4\dbch\af31505\loch\f4 + do not align to the reference genome have already been removed, as well as chimeric ambiguous reads (see Section II.a.2 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 +\hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014 for a definition of chimeric ambiguous reads). In addition, d\hich\af4\dbch\af31505\loch\f4 +uplicate reads (reads where both ends align to within +/- 4bp of each other) have been removed as well (see Section II.a.3 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 +\hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014 for a full description of duplicate removal). Full details \hich\af4\dbch\af31505\loch\f4 +of the Hi-C processing pipeline used in this study are provided in Section II.a. of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 +\af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid687952 \hich\af4\dbch\af31505\loch\f4 , Cell 2014.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 Each line of the merged_nodups file represents a single Hi-C read pair that has passed the alignme\hich\af4\dbch\af31505\loch\f4 nt and duplicate removal stages. The format of each line of the file is: +\par +\par }\pard \ltrpar\ql \li0\ri0\nowidctlpar\wrapdefault\faauto\rin0\lin0\itap0 {\rtlch\fcs1 \af39\afs24 \ltrch\fcs0 \f39\fs24\cf17\insrsid9332599 \hich\af39\dbch\af31505\loch\f39 read_name \~ \~strand1 \~ \~chromosome1 \~ \~position1 \~ \~fragment-index1 \~ \~ +strand2 \~ \~chromosome2 \~ \~position2 \~ \~fragment-index2 \~ \~mapq1 \~ \~mapq2}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par }\pard \ltrpar\ql \li0\ri0\nowidctlpar\tx720\tx1440\tx2160\tx2880\tx3600\tx4320\tx5040\tx5760\tx6480\tx7200\tx7920\tx8640\wrapdefault\faauto\rin0\lin0\itap0 {\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par \hich\af4\dbch\af31505\loch\f4 where: +\par \hich\af4\dbch\af31505\loch\f4 read_name = the name of the read pair as seen in the FASTQ files +\par \hich\af4\dbch\af31505\loch\f4 strand = the strand that the read maps to (0=forward, 16=reverse) +\par \hich\af4\dbch\af31505\loch\f4 chromosome = the chromosome that the read maps to ([1-22,X,Y,MT] for human (b37 reference genome) or [chr1-chr19,chrX,chrY,ch\hich\af4\dbch\af31505\loch\f4 rM] for mouse (mm9 reference genome)) +\par \hich\af4\dbch\af31505\loch\f4 position = the position on the chromosome that the read maps to +\par \hich\af4\dbch\af31505\loch\f4 fragment-index = the index of the interval demarcated by restrictions sites in the genome, starting with 0 for the interval preceding the first restrictio\hich\af4\dbch\af31505\loch\f4 n site +\par \hich\af4\dbch\af31505\loch\f4 mapq = the mapping quality score returned by BWA (see Section II.a.1 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 +et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014 for full details about the alignment process) +\par +\par }{\rtlch\fcs1 \ab\ai\af4\afs24 \ltrch\fcs0 \b\i\f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 Contact matrices and Associated Normalization and Expected \hich\af4\dbch\af31505\loch\f4 Vectors:}{\rtlch\fcs1 \ab\af4\afs24 \ltrch\fcs0 +\b\f4\fs24\insrsid9332599 +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par \hich\af4\dbch\af31505\loch\f4 +Under the main series record (GSE63525), there are a set of tar archives that contain the raw observed intra-chromosomal or inter-chromosomal contact matrices for each cell type analyzed in our study as well as normalization vectors to transform +\hich\af4\dbch\af31505\loch\f4 the raw matrices into normalized matrices and 1-d expected vectors to transform the observed matrices into O/E matrices (see the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell, 2014 for details). +\par +\par \hich\af4\dbch\af31505\loch\f4 The intrachromosomal contact matrix archives\hich\af4\dbch\af31505\loch\f4 + contain intrachromosomal contact matrices at 8 (9 for GM12878_combined) different base pair delimited resolutions (1 Mb, 500kb, 250kb, 100kb, 50kb, 25kb, 10kb, 5kb [and 1kb for GM12878_combined]). At each resolution, files associated with each chromosome +\hich\af4\dbch\af31505\loch\f4 \hich\af4\dbch\af31505\loch\f4 +are provided in a separate subdirectory. Within, each chromosome subdirectory, there are two further subdirectories (MAPQG0 and MAPQGE30). The MAPQG0 subdirectory contains files associated with the contact matrices constructed from all read pairs that uni +\hich\af4\dbch\af31505\loch\f4 q\hich\af4\dbch\af31505\loch\f4 uely align to the genome (MAPQ>0). The MAPQGE30 subdirectory contains files associated with the contact matrices constructed from all read pairs that map}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid687952 \hich\af4\dbch\af31505\loch\f4 to the genome with a MAPQ>=30.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 For example, the files associated with the contact matrix for chromos\hich\af4\dbch\af31505\loch\f4 ome 1 at 5 kb resolution using MAPQ>=30 read pairs are in the subdirectory: +\par +\par \hich\af4\dbch\af31505\loch\f4 CELL_TYPE/5kb_resolution_intrachromosomal/chr1/MAPQGE30/ +\par +\par \hich\af4\dbch\af31505\loch\f4 There are 7 text files associated with each intrachromosomal contact matrix ([CHR] represents the chromosome number and [\hich\af4\dbch\af31505\loch\f4 RES] represents the resolution): +\par +\par \hich\af4\dbch\af31505\loch\f4 [CHR]_[RES].RAWobserved +\par \hich\af4\dbch\af31505\loch\f4 [CHR]_[RES].KRnorm +\par \hich\af4\dbch\af31505\loch\f4 [CHR]_[RES].VCnorm +\par \hich\af4\dbch\af31505\loch\f4 [CHR]_[RES].SQRTVCnorm +\par \hich\af4\dbch\af31505\loch\f4 [CHR]_[RES].RAWexpected +\par \hich\af4\dbch\af31505\loch\f4 [CHR]_[RES].KRexpected +\par \hich\af4\dbch\af31505\loch\f4 [CHR]_[RES].VCexpected +\par \hich\af4\dbch\af31505\loch\f4 [CHR]_[RES].SQRTVCexpected +\par +\par \hich\af4\dbch\af31505\loch\f4 For example, th\hich\af4\dbch\af31505\loch\f4 e files associated with the contact matrix for chromosome 1 at 5 kb resolution using MAPQ>=30 read pairs are: +\par +\par \hich\af4\dbch\af31505\loch\f4 CELL_TYPE/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.RAWobserved +\par \hich\af4\dbch\af31505\loch\f4 CELL_TYPE/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.KRn\hich\af4\dbch\af31505\loch\f4 orm +\par \hich\af4\dbch\af31505\loch\f4 CELL_TYPE/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.VCnorm +\par \hich\af4\dbch\af31505\loch\f4 CELL_TYPE/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.SQRTVCnorm +\par \hich\af4\dbch\af31505\loch\f4 CELL_TYPE/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.RAWexpected +\par \hich\af4\dbch\af31505\loch\f4 CELL_TYPE/5kb_resolution_in\hich\af4\dbch\af31505\loch\f4 trachromosomal/chr1/MAPQGE30/chr1_5kb.KRexpected +\par \hich\af4\dbch\af31505\loch\f4 CELL_TYPE/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.VCexpected +\par \hich\af4\dbch\af31505\loch\f4 CELL_TYPE/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.SQRTVCexpected +\par +\par \hich\af4\dbch\af31505\loch\f4 *.RAWobserved is a text file with the raw observed\hich\af4\dbch\af31505\loch\f4 + contact matrix in sparse matrix notation. Each line has three fields: i, j, and M_i,j. (i and j are written as the left edge of the bin at a given resolution; for example, at 100 kb resolution, the entry corresponding to the first row and tenth column of +\hich\af4\dbch\af31505\loch\f4 \hich\af4\dbch\af31505\loch\f4 the matrix would correspond to M_i,j, where i=0, j=900000). Only the upper triangle of the matrix is provided (i.e. i<=j), the matrix }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid687952 \hich\af4\dbch\af31505\loch\f4 is symmetric, so M_i,j = M_j,i.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 The three *norm files are normalization vectors that can be used to transform the raw co\hich\af4\dbch\af31505\loch\f4 +ntact matrices M into normalized matrices M*. (See the glossary below and section II.b of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{ +\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell, 2014 for more information about the different types of normalizations. All analyses and results pre\hich\af4\dbch\af31505\loch\f4 +sented in the main text of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +, Cell, 2014 were performed using KR normalized contact matrices.) Each file is ordered such that the first line of the normalization vector file is the norm factor for the first row/column of the corresponding\hich\af4\dbch\af31505\loch\f4 + raw contact matrix, the second line is the factor for the second row/column of the contact matrix, and so on. To normalize, an entry M_i,j in a *RAWobserved file, divide the entry by the correspo}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid687952 \hich\af4\dbch\af31505\loch\f4 nding norm factors for i and j.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 For example, here is a lin\hich\af4\dbch\af31505\loch\f4 e from the GM12878_combined 5kb chr1 MAPQGE30 raw observed contact matrix (GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.RAWobserved): +\par }\pard \ltrpar\ql \li0\ri0\nowidctlpar\tx560\tx1120\tx1680\tx2240\tx2800\tx3360\tx3920\tx4480\tx5040\tx5600\tx6160\tx6720\wrapdefault\faauto\rin0\lin0\itap0 {\rtlch\fcs1 \af40 \ltrch\fcs0 \f40\insrsid9332599 \hich\af40\dbch\af31505\loch\f40 40000000\tab +40100000\tab 59.0 +\par +\par }\pard \ltrpar\ql \li0\ri0\nowidctlpar\tx720\tx1440\tx2160\tx2880\tx3600\tx4320\tx5040\tx5760\tx6480\tx7200\tx7920\tx8640\wrapdefault\faauto\rin0\lin0\itap0 {\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +To normalize this entry using the KR normalization vector, one would di\hich\af4\dbch\af31505\loch\f4 +vide 59.0 by the 8001st line ((40000000/5000)+1=8001) and the 8021st line ((40100000/5000)+1=8021) of GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.KRnorm. The 8001st line of the KR norm file is }{\rtlch\fcs1 \af40 \ltrch\fcs0 +\f40\insrsid9332599 \hich\af40\dbch\af31505\loch\f40 1.2988778370674694;}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 The 8021st line \hich\af4\dbch\af31505\loch\f4 of the KR norm file is }{\rtlch\fcs1 \af40 +\ltrch\fcs0 \f40\insrsid9332599 \hich\af40\dbch\af31505\loch\f40 1.6080499717941548. }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 So the corresponding KR normalized entry for the entry above is }{\rtlch\fcs1 +\af40 \ltrch\fcs0 \f40\insrsid9332599 \hich\af40\dbch\af31505\loch\f40 59.0/(1.2988778370674694*1.6080499717941548) }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 or }{\rtlch\fcs1 \af40 \ltrch\fcs0 +\f40\insrsid9332599 \hich\af40\dbch\af31505\loch\f40 28.24776973966101. }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 There will be some entries in the KR vector files which are NaNs \hich\f4 \endash \loch\f4 + these correspon\hich\af4\dbch\af31505\loch\f4 d to rows which were too sparse and were thrown out before normalization was performed (See Section II.b.4 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014). If the KR normalization vector file is completely empty or all NaNs, then +\hich\af4\dbch\af31505\loch\f4 the KR algorithm didn\hich\f4 \rquote \loch\f4 t converge on that particular matrix (likely due to sparsity of the matrix). In that case, one can use either the VC or SQRTVC normalizations or check a different resolution.}{ +\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid687952 \hich\af4\dbch\af31505\loch\f4 }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 }{\rtlch\fcs1 \af40 \ltrch\fcs0 \f40\insrsid9332599 +\par +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +The four *expected files are expected vectors that can be used to construct O/E matrices that account for the increased number of contacts seen at short distances due to random polymer interactions driven by one-dimensional genome proximity (see the gloss +\hich\af4\dbch\af31505\loch\f4 a\hich\af4\dbch\af31505\loch\f4 ry below and section II.c of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{ +\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +, Cell, 2014 for more information about the construction of these expected vectors and O/E matrices). Note that these expected vectors only account for random polymer i\hich\af4\dbch\af31505\loch\f4 +nteractions driven by one-dimensional genome proximity and do not control for other features such as compartmentalization or contact domain structure. As such, they are not appropriate expected models when seeking to identify focal looping interactions. I +\hich\af4\dbch\af31505\loch\f4 n\hich\af4\dbch\af31505\loch\f4 identifying focal looping interactions, one must use local expecteds (see Section VI.a.4.i, Section VI.a.5.i, and Figure 3 of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +, Cell 2014). These expected files are ordered such that first line of the expected vector file is the expecte\hich\af4\dbch\af31505\loch\f4 d number of contacts between two loci separated by 0*RES base pairs (0}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\super\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 th}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 + diagonal of contact matrix), the second line of the file is the expected number of contacts between two loci separated by 1*RES base pairs (1}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\super\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 st}{ +\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 diagonal of contact matrix), and so on.\hich\af4\dbch\af31505\loch\f4 So to create the O/E matrix, divide each entry M_i,j by the expected value cor}{\rtlch\fcs1 +\af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid687952 \hich\af4\dbch\af31505\loch\f4 responding\hich\af4\dbch\af31505\loch\f4 to the distance j-i.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 For example, for the above entry of the GM12878_combined 5kb chr1 MAPQGE30 raw observed contact matrix, to get the corresponding entry of the O\hich\af4\dbch\af31505\loch\f4 +/E matrix divide by the 21st line (((41000000-40000000)/5000)+1=21) of GM12878_combined/5kb_resolution_intrachromosomal/chr1/MAPQGE30/chr1_5kb.RAWexpected. The 21st line of the raw expected file is }{\rtlch\fcs1 \af40 \ltrch\fcs0 \f40\insrsid9332599 +\hich\af40\dbch\af31505\loch\f40 20.101675. }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 So the corresponding raw O/E entry for the entr\hich\af4\dbch\af31505\loch\f4 y above is }{\rtlch\fcs1 \af40 +\ltrch\fcs0 \f40\insrsid9332599 \hich\af40\dbch\af31505\loch\f40 59.0/20.101675 or 2.935078793185145. }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +To create the normalized O/E files, first construct the normalized observed matrices as above and then divide by the corresponding line of the normalized expected file (i.e. *.KRexpected, *.VCexpected, or *.S\hich\af4\dbch\af31505\loch\f4 QRTVCexpected). + +\par +\par \hich\af4\dbch\af31505\loch\f4 +The interchromosomal contact matrix archives contain interchromosomal contact matrices at 8 different base pair delimited resolutions (1 Mb, 500kb, 250kb, 100kb, 50kb, 25kb, 10kb, 5kb). At each resolution, the files associated with each p +\hich\af4\dbch\af31505\loch\f4 +air of chromosomes are provided in a separate subdirectory. Within each chromosome pair subdirectory, there are two further subdirectories (MAPQG0 and MAPQGE30). The MAPQG0 subdirectory contains files associated with the contact matrices constructed from +\hich\af4\dbch\af31505\loch\f4 a\hich\af4\dbch\af31505\loch\f4 +ll read pairs that uniquely align to the genome (MAPQ>0). The MAPQGE30 subdirectory contains files associated with the contact matrices constructed from all read pairs that map to the genome with a MAPQ>=30. +\par +\par \hich\af4\dbch\af31505\loch\f4 For example, the files associated with the cont\hich\af4\dbch\af31505\loch\f4 act matrix for chromosome 1 and chromosome 2 using MAPQ>=30 read pairs are in the subdirectory: +\par +\par \hich\af4\dbch\af31505\loch\f4 CELL_TYPE/100kb_resolution_interchromosomal/chr1_chr2/MAPQGE30/ +\par +\par \hich\af4\dbch\af31505\loch\f4 There are 15 text files associated with each interchromosomal contact matrix ([CHR1] represent\hich\af4\dbch\af31505\loch\f4 +s the first chromosome number, [CHR2] represents the second chromosome number, and [RES] represents the resolution): +\par +\par \hich\af4\dbch\af31505\loch\f4 [CHR1]_[CHR2]_[RES].RAWobserved +\par \hich\af4\dbch\af31505\loch\f4 [CHR1]_[RES].KRnorm +\par \hich\af4\dbch\af31505\loch\f4 [CHR1]_[RES].VCnorm +\par \hich\af4\dbch\af31505\loch\f4 [CHR1]_[RES].SQRTVCnorm}{\rtlch\fcs1 \af40 \ltrch\fcs0 \f40\insrsid9332599 +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 [CHR1]_[RES].INTERKRnorm}{\rtlch\fcs1 \af40 \ltrch\fcs0 \f40\insrsid9332599 +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 [CHR1]_[RES].INTE\hich\af4\dbch\af31505\loch\f4 RVCnorm +\par \hich\af4\dbch\af31505\loch\f4 [CHR1]_[RES].GWKRnorm +\par \hich\af4\dbch\af31505\loch\f4 [CHR1]_[RES].GWVCnorm +\par \hich\af4\dbch\af31505\loch\f4 [CHR2]_[RES].KRnorm +\par \hich\af4\dbch\af31505\loch\f4 [CHR2]_[RES].VCnorm +\par \hich\af4\dbch\af31505\loch\f4 [CHR2]_[RES].SQRTVCnorm}{\rtlch\fcs1 \af40 \ltrch\fcs0 \f40\insrsid9332599 +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 [CHR2]_[RES].INTERKRnorm}{\rtlch\fcs1 \af40 \ltrch\fcs0 \f40\insrsid9332599 +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 [CHR2]_[RES].INTERVCnorm +\par \hich\af4\dbch\af31505\loch\f4 [CHR2]_[RES].GWKRnorm +\par \hich\af4\dbch\af31505\loch\f4 [CHR2]_[RES].GWVCnorm +\par +\par \hich\af4\dbch\af31505\loch\f4 For example, the files associated with the contact matrix for chromosome 1 and chromosome 2 using MAPQ>=30 read pairs are: +\par +\par \hich\af4\dbch\af31505\loch\f4 chr1_2_100kb.RAWobserved +\par \hich\af4\dbch\af31505\loch\f4 chr1_100kb.KRnorm +\par \hich\af4\dbch\af31505\loch\f4 chr1_100kb.VCnorm +\par \hich\af4\dbch\af31505\loch\f4 chr1_100kb.SQRTVCnorm}{\rtlch\fcs1 \af40 \ltrch\fcs0 \f40\insrsid9332599 +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 chr1_100kb.INTERKRnorm}{\rtlch\fcs1 \af40 \ltrch\fcs0 \f40\insrsid9332599 +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 chr1_100kb.INTERVCnorm +\par \hich\af4\dbch\af31505\loch\f4 chr\hich\af4\dbch\af31505\loch\f4 1_100kb.GWKRnorm +\par \hich\af4\dbch\af31505\loch\f4 chr1_100kb.GWVCnorm +\par \hich\af4\dbch\af31505\loch\f4 chr2_100kb.KRnorm +\par \hich\af4\dbch\af31505\loch\f4 chr2_100kb.VCnorm +\par \hich\af4\dbch\af31505\loch\f4 chr2_100kb.SQRTVCnorm}{\rtlch\fcs1 \af40 \ltrch\fcs0 \f40\insrsid9332599 +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 chr2_100kb.INTERKRnorm}{\rtlch\fcs1 \af40 \ltrch\fcs0 \f40\insrsid9332599 +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 chr2_100kb.INTERVCnorm +\par \hich\af4\dbch\af31505\loch\f4 chr2_100kb.GWKRnorm +\par \hich\af4\dbch\af31505\loch\f4 chr2_100kb.GWVCnorm +\par +\par \hich\af4\dbch\af31505\loch\f4 At higher resolutions and for some cell types, INTERKR/VC files and GWKR/V\hich\af4\dbch\af31505\loch\f4 C files are not available, so }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid5574019 +\hich\af4\dbch\af31505\loch\f4 only 9 text files are provided.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 The *.RAWobserved files for the interchromosomal matrices are formatted the same way as the intrachromosomal matrices above except the i locus corresponds to CHR1 and the j locus corresponds t\hich\af4\dbch\af31505\loch\f4 +o CHR2. One can create the normalized matrices as above except one should use the line corresponding to the i locus norm factor from the CHR1 normalization vector file and the line corresponding to the j locus norm factor from the CHR2 normalization vecto +\hich\af4\dbch\af31505\loch\f4 r\hich\af4\dbch\af31505\loch\f4 file. (See the glossary below and section II.b of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 +\hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell, 2014 for more information about the different types of normalizations.) +\par +\par }{\rtlch\fcs1 \ab\ai\af4\afs24 \ltrch\fcs0 \b\i\f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 Loop Annotation Files: +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +Under the main Series Record (GSE63525), there are files named *_HiCCUPS_looplist.txt.gz or *_HiCCUPS_looplist_with_motifs.txt.gz, where * represents each of the cell types analyzed in this study (GM12878, HMEC, HUVEC, HeLa, IMR90, K562, KBM7, NHEK, CH12- +\hich\af4\dbch\af31505\loch\f4 L\hich\af4\dbch\af31505\loch\f4 +X), as well as biological replicate annotations for GM12878 (GM12878_primary and GM12878_replicate). These files contain Juicebox-loadable (www.aidenlab.org/juicebox) loop annotations returned by our loop calling algorithm, HiCCUPS (see Fig. 3, the Experi +\hich\af4\dbch\af31505\loch\f4 m\hich\af4\dbch\af31505\loch\f4 ental Procedures, and Section VI.a.5 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 +et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014). These files contain a header line, followed by a line for every loop. The files named *_HiCCUPS_looplist.txt.gz contain 20 fields per line in t +\hich\af4\dbch\af31505\loch\f4 he following format: +\par +\par \hich\af4\dbch\af31505\loch\f4 +chromosome1 x1 x2 chromosome2 y1 y2 color observed expected_bottom_left expected_donut expected_horizontal expected_vertical fdr_bottom_left fdr_donut fdr_horizontal fdr_vertical number_ +\hich\af4\dbch\af31505\loch\f4 collapsed centroid1 centroid2 radius +\par +\par \hich\af4\dbch\af31505\loch\f4 Explanations of each field are as follows: +\par \hich\af4\dbch\af31505\loch\f4 chromosome = the chromosome that the loop is located on +\par \hich\af4\dbch\af31505\loch\f4 x1,x2 = the coordinates of the upstream locus corresponding to the peak pixel (see the Experimental Procedures\hich\af4\dbch\af31505\loch\f4 and VI.a.5.iv of the Extended Experimental Procedures of Rao, Huntley, }{ +\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014 for a definition of the peak pixel) +\par \hich\af4\dbch\af31505\loch\f4 y1,y2 = the coordinates of the downstream locus corresponding to the peak pixel (see the Experimental Procedures and VI.a.5.iv of t\hich\af4\dbch\af31505\loch\f4 he Extended Experimental Procedures of Rao, Huntley, }{ +\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014 for a definition of the peak pixel) +\par \hich\af4\dbch\af31505\loch\f4 color = the color that the feature will be rendered as if loaded in Juicebox (www.aidenlab.org/juicebox) +\par \hich\af4\dbch\af31505\loch\f4 observed = the raw observed counts at the pea\hich\af4\dbch\af31505\loch\f4 k pixel (see the Experimental Procedures and VI.a.5.iv of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 +\ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014 for a definition of the peak pixel) +\par \hich\af4\dbch\af31505\loch\f4 expected_[bottom_left, donut, horizontal, vertical] = the expected counts calculated using \hich\af4\dbch\af31505\loch\f4 +the [bottom_left, donut, horizontal, vertical] filter (see Figure 3 and section VI.a.5.i of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{ +\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014) +\par \hich\af4\dbch\af31505\loch\f4 fdr_[bottom_left, donut, horizontal, vertical] = the q-value of the loop calculated using th\hich\af4\dbch\af31505\loch\f4 +e [bottom_left, donut, horizontal, vertical] filter (see VI.a.5.ii of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 +\ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014) +\par \hich\af4\dbch\af31505\loch\f4 number_collapsed = the number of pixels that were clustered together as part of the loop call (see section VI.a.5.\hich\af4\dbch\af31505\loch\f4 iv of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 +\af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014) +\par \hich\af4\dbch\af31505\loch\f4 centroid1 = the upstream coordinate of the centroid of the cluster of pixels corresponding to the loop (see section VI.a.5.iv of the Extended Experimental Procedures of Rao, Hunt\hich\af4\dbch\af31505\loch\f4 ley, }{ +\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014) +\par \hich\af4\dbch\af31505\loch\f4 centroid2 = the downstream coordinate of the centroid of the cluster of pixels corresponding to the loop (see section VI.a.5.iv of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014) +\par \hich\af4\dbch\af31505\loch\f4 radius = the Euclidean distanc\hich\af4\dbch\af31505\loch\f4 +e from the centroid of the cluster of pixels to the farthest pixel in the cluster of pixels (see section VI.a.5.iv of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 +\hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014) +\par +\par \hich\af4\dbch\af31505\loch\f4 The files named *_HiCCUPS_looplist_with_motifs.txt.gz contain 30 \hich\af4\dbch\af31505\loch\f4 fields per line. The first 20 are the same as above, followed by an additional 10 in the following format: +\par +\par \hich\af4\dbch\af31505\loch\f4 motif_x1 motif_x2 sequence1 orientation1 uniqueness1 motif_y1 motif_y2 sequence2 orientation2 uniqueness2 +\par +\par \hich\af4\dbch\af31505\loch\f4 Explanations o\hich\af4\dbch\af31505\loch\f4 f each field are as follows: +\par \hich\af4\dbch\af31505\loch\f4 motif_x1,x2 = the start and end coordinates of the localized CTCF motif within the upstream loop anchor (see Section VI.e.7 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014). +\par \hich\af4\dbch\af31505\loch\f4 sequence1 = the seq\hich\af4\dbch\af31505\loch\f4 uence of the localized CTCF motif within the upstream loop anchor +\par \hich\af4\dbch\af31505\loch\f4 orientation1 = the orientation of the localized CTCF motif within the upstream loop anchor; p\hich\f4 \rquote \loch\f4 if the motif sequence is on the forward strand and \hich\f4 \rquote \loch\f4 n\hich\f4 \rquote \loch\f4 + if the motif sequence is on the reverse \hich\af4\dbch\af31505\loch\f4 strand +\par \hich\af4\dbch\af31505\loch\f4 uniqueness1 = whether the localized CTCF motif within the upstream loop anchor was uniquely called (\hich\f4 \lquote \loch\f4 u\hich\f4 \rquote \loch\f4 +; see Section VI.e.7 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\hich\af4\dbch\af31505\loch\f4 , Cell 2014) or inferred based on the convergent orientation pr\hich\af4\dbch\af31505\loch\f4 inciple (\hich\f4 \lquote \loch\f4 i\hich\f4 \rquote \loch\f4 +; see Section VI.e.8 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\hich\af4\dbch\af31505\loch\f4 , Cell 2014) +\par \hich\af4\dbch\af31505\loch\f4 motif_y1,y2; sequence2; orientation2; and uniqueness2 are the same as above except for the downstream loop anchor. +\par +\par \hich\af4\dbch\af31505\loch\f4 If the fields are \hich\f4 \lquote \loch\f4 NA\hich\f4 \rquote \loch\f4 that ind\hich\af4\dbch\af31505\loch\f4 +icates that we were unable to localize the anchor to a single CTCF motif. Motifs were called using STORM (Schones, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , 2007) using the following CTCF position weight matrix from Kim, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 +\ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , 2007: +\par }\pard \ltrpar\ql \li0\ri0\nowidctlpar\tx560\tx1120\tx1680\tx2240\tx2800\tx3360\tx3920\tx4480\tx5040\tx5600\tx6160\tx6720\wrapdefault\faauto\rin0\lin0\itap0 {\rtlch\fcs1 \af40 \ltrch\fcs0 \f40\insrsid9332599 +\par \hich\af40\dbch\af31505\loch\f40 P0 A C G T +\par \hich\af40\dbch\af31505\loch\f40 00 60 47 \hich\af40\dbch\af31505\loch\f40 69 53 +\par \hich\af40\dbch\af31505\loch\f40 01 0 82 40 107 +\par \hich\af40\dbch\af31505\loch\f40 02 46 41 103 39 +\par \hich\af40\dbch\af31505\loch\f40 03 77 0 152 0 +\par \hich\af40\dbch\af31505\loch\f40 04 0 229 0 0 +\par \hich\af40\dbch\af31505\loch\f40 05 0 229 0 0 +\par \hich\af40\dbch\af31505\loch\f40 06 171 0 30 28 +\par \hich\af40\dbch\af31505\loch\f40 07 18 112 99 \hich\af40\dbch\af31505\loch\f40 0 +\par \hich\af40\dbch\af31505\loch\f40 08 27 144 19 39 +\par \hich\af40\dbch\af31505\loch\f40 09 229 0 0 0 +\par \hich\af40\dbch\af31505\loch\f40 10 0 0 229 0 +\par \hich\af40\dbch\af31505\loch\f40 11 111 0 118 0 +\par \hich\af40\dbch\af31505\loch\f40 12 0 0 142 87 +\par \hich\af40\dbch\af31505\loch\f40 13 0 0 229 0 +\par \hich\af40\dbch\af31505\loch\f40 14 0 0 229 0 +\par \hich\af40\dbch\af31505\loch\f40 15 36 171 0 22 +\par \hich\af40\dbch\af31505\loch\f40 16 88 0 127 14 +\par \hich\af40\dbch\af31505\loch\f40 17 0 135 94 0 +\par \hich\af40\dbch\af31505\loch\f40 18 37 96 32 64 +\par \hich\af40\dbch\af31505\loch\f40 19 72 74 70 13 +\par +\par }{\rtlch\fcs1 \ab\ai\af4\afs24 \ltrch\fcs0 \b\i\f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 Contact Domain Annotation Files:}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par }\pard \ltrpar\ql \li0\ri0\nowidctlpar\tx720\tx1440\tx2160\tx2880\tx3600\tx4320\tx5040\tx5760\tx6480\tx7200\tx7920\tx8640\wrapdefault\faauto\rin0\lin0\itap0 {\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +Under the main Series Record (GSE63525), there \hich\af4\dbch\af31505\loch\f4 +are files named *_Arrowhead_domainlist.txt.gz where * represents each of the cell types analyzed in this study (GM12878, HMEC, HUVEC, HeLa, IMR90, K562, KBM7, NHEK, CH12-LX). These files contain Juicebox-loadable (www.aidenlab.org/juicebox) domain annotat +\hich\af4\dbch\af31505\loch\f4 i\hich\af4\dbch\af31505\loch\f4 ons returned by our domain calling algorithm, Arrowhead (see Fig. 2, the Experimental Procedures, and Section IV.a. of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 +\af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et a\hich\af4\dbch\af31505\loch\f4 l.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +, Cell 2014). These files contain a header line, followed by a line for every \hich\af4\dbch\af31505\loch\f4 domain. These files contain 12 fields per line in the following format: +\par +\par \hich\af4\dbch\af31505\loch\f4 chromosome1 x1 x2 chromosome2 y1 y2 color corner_score Uvar Lvar Usign Lsign +\par +\par \hich\af4\dbch\af31505\loch\f4 Explanations of each field are as follows: +\par \hich\af4\dbch\af31505\loch\f4 chromosome = the chromosome t\hich\af4\dbch\af31505\loch\f4 hat the domain is located on +\par \hich\af4\dbch\af31505\loch\f4 x1,x2/y1,y2 = the interval spanned by the domain (contact domains manifest as squares on the diagonal of a Hi-C matrix and as such: x1=y1, x2=y2) +\par \hich\af4\dbch\af31505\loch\f4 color = the color that the feature will be rendered as if loaded in Juicebox (www\hich\af4\dbch\af31505\loch\f4 .aidenlab.org/juicebox) +\par \hich\af4\dbch\af31505\loch\f4 +corner_score = the corner score, a score indicating the likelihood that a pixel is at the corner of a contact domain. Higher values indicate a greater likelihood of being at the corner of a domain (see Section IV.a.3 of the Extended +\hich\af4\dbch\af31505\loch\f4 Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\hich\af4\dbch\af31505\loch\f4 , Cell 2014) +\par \hich\af4\dbch\af31505\loch\f4 Uvar = the variance of the upper triangle +\par \hich\af4\dbch\af31505\loch\f4 Lvar = the variance of the lower triangle +\par \hich\af4\dbch\af31505\loch\f4 Usign = -1*(sum of the sign of the entries in the upper triangle) +\par \hich\af4\dbch\af31505\loch\f4 Lsign = sum of the sign of the entries in the\hich\af4\dbch\af31505\loch\f4 lower triangle +\par +\par \hich\af4\dbch\af31505\loch\f4 Corner pixels which had both their left and right edges match to within 5 bins were merged to a single block call. In this case, the scores \hich\f4 \endash \hich\af4\dbch\af31505\loch\f4 + given by the last 5 columns - are the mean of the all the corner pixels in the merged group, and the edges are given by the largest (in bp) values called for each edge. (See Section IV.a.3 of the Extended Experimental Procedures of Rao, Huntley, }{ +\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , C\hich\af4\dbch\af31505\loch\f4 +ell 2014 for details about these scores.) +\par +\par }{\rtlch\fcs1 \ab\ai\af4\afs24 \ltrch\fcs0 \b\i\f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 Subcompartment Annotation File: +\par }\pard \ltrpar\ql \li0\ri0\nowidctlpar\wrapdefault\faauto\rin0\lin0\itap0 {\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 GSE63525_GM12878_subcompartments.bed.gz}{\rtlch\fcs1 \af39\afs24 \ltrch\fcs0 +\f39\fs24\insrsid9332599 \hich\af39\dbch\af31505\loch\f39 contains the GM12878 annotation of the locations of the six subcompartments (A1, A2, B1, B2, B3, B4) identified in this study (see Section V.\hich\af39\dbch\af31505\loch\f39 +a.2 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af39\afs24 \ltrch\fcs0 \f39\fs24\insrsid14188250 \hich\af39\dbch\af31505\loch\f39 et al.}{\rtlch\fcs1 \af39\afs24 \ltrch\fcs0 \f39\fs24\insrsid9332599 +\hich\af39\dbch\af31505\loch\f39 , Cell 2014 for details regarding the clustering algorithm). The file is a bed file; the name of the subcompartment (A1, A2, B1, B2, B3, B4) is provided in the name field of the bed file for +\hich\af39\dbch\af31505\loch\f39 each entry. NA is used in the name field for loci that could not be assigned to a subcompartment. An annotation of the six subcompartments is only provided for GM12878 as our other maps were too sparse to rel}{ +\rtlch\fcs1 \af39\afs24 \ltrch\fcs0 \f39\fs24\insrsid5574019 \hich\af39\dbch\af31505\loch\f39 iably annotate subcompartments.}{\rtlch\fcs1 \af39\afs24 \ltrch\fcs0 \f39\fs24\insrsid9332599 +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par }{\rtlch\fcs1 \ab\ai\af4\afs24 \ltrch\fcs0 \b\i\f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 Superloop Ann\hich\af4\dbch\af31505\loch\f4 otation File: +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 GSE63525_GM12878_HiCCUPS_chrX_superloop_list.txt.gz}{\rtlch\fcs1 \af39\afs24 \ltrch\fcs0 \f39\fs24\insrsid9332599 \hich\af39\dbch\af31505\loch\f39 + contains the GM12878 annotation of super loops on chromosome X. The file is in the same format as the loop annotati}{\rtlch\fcs1 \af39\afs24 \ltrch\fcs0 \f39\fs24\insrsid5574019 \hich\af39\dbch\af31505\loch\f39 ons (20 fields per line) above.}{ +\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par }\pard \ltrpar\ql \li0\ri0\nowidctlpar\tx720\tx1440\tx2160\tx2880\tx3600\tx4320\tx5040\tx5760\tx6480\tx7200\tx7920\tx8640\wrapdefault\faauto\rin0\lin0\itap0 {\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par }\pard \ltrpar\ql \li0\ri0\nowidctlpar\tx560\tx1120\tx1680\tx2240\tx2800\tx3360\tx3920\tx4480\tx5040\tx5600\tx6160\tx6720\wrapdefault\faauto\rin0\lin0\itap0 {\rtlch\fcs1 \ab\ai\af4\afs24 \ltrch\fcs0 \b\i\f4\fs24\insrsid9332599 +\hich\af4\dbch\af31505\loch\f4 SNP File:}{\rtlch\fcs1 \ai\af4\afs24 \ltrch\fcs0 \i\f4\fs24\insrsid9332599 +\par }\pard \ltrpar\ql \li0\ri0\nowidctlpar\wrapdefault\faauto\rin0\lin0\itap0 {\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +GSE63525_GM12878_SNPs.txt.gz contains the GM12878 SNPs used to generate the diploid Hi-C maps produced in this study (see VII.a. for details about how this SNP list was generated). Each row of the text file represents one SNP and contains three fields: + +\par +\par \hich\af4\dbch\af31505\loch\f4 c\hich\af4\dbch\af31505\loch\f4 hr:position paternal_nucleotide maternal_nucleotide +\par +\par \hich\af4\dbch\af31505\loch\f4 \hich\f4 For example, the first line is 1:63697 C T indicating that this is the SNP on chromosome 1, position 63697, and that the paternal chromosome will have the nucleotide \'93\loch\f4 \hich\f4 C\'94\loch\f4 + at this position, and the materna\hich\af4\dbch\af31505\loch\f4 \hich\f4 l chromosome will have the nucleotide \'93\loch\f4 \hich\f4 T\'94\loch\f4 + at this position. Contact matrices for GM12878 maternal and paternal homologs generated using this SNP list are provided in the tar archive \hich\f4 \lquote \loch\f4 GSE63525_GM12878_diploid_intrachromosomal_contact_matrices.tar.gz\hich\f4 \rquote +\loch\f4 . Cont\hich\af4\dbch\af31505\loch\f4 a\hich\af4\dbch\af31505\loch\f4 ct matrices are provided in the format specified above. +\par }\pard \ltrpar\ql \li0\ri0\nowidctlpar\tx560\tx1120\tx1680\tx2240\tx2800\tx3360\tx3920\tx4480\tx5040\tx5600\tx6160\tx6720\wrapdefault\faauto\rin0\lin0\itap0 {\rtlch\fcs1 \ab\ai\af4\afs24 \ltrch\fcs0 \b\i\f4\fs24\insrsid9332599 +\hich\af4\dbch\af31505\loch\f4 }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par }\pard \ltrpar\ql \li0\ri0\nowidctlpar\tx720\tx1440\tx2160\tx2880\tx3600\tx4320\tx5040\tx5760\tx6480\tx7200\tx7920\tx8640\wrapdefault\faauto\rin0\lin0\itap0 {\rtlch\fcs1 \ab\ai\af4\afs24 \ltrch\fcs0 \b\i\f4\fs24\insrsid9332599 +\hich\af4\dbch\af31505\loch\f4 GLOSSARY: +\par }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par \hich\af4\dbch\af31505\loch\f4 KRnorm = normalization vector obtained using the matrix balancing procedure of Knight and Ruiz on the intrachromosomal contact matrix, as reimplemented by us in Java. See Knight & Ruiz, \hich\af4\dbch\af31505\loch\f4 +IMA Journal of Numerical Analysis, 2012; section II.b.4 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell, 2014. Normalization factors are scaled such that the sum of the entries in the normalized contact matrix is equal to the sum of th\hich\af4\dbch\af31505\loch\f4 e ent}{\rtlch\fcs1 \af4\afs24 +\ltrch\fcs0 \f4\fs24\insrsid5574019 \hich\af4\dbch\af31505\loch\f4 ries in the raw contact matrix.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 GWKRnorm = normalization vector obtained using the matrix balancing procedure of Knight and Ruiz on the entire genome-wide contact matrix (i.e. all intrachromosomal and interchromosomal contact matrices), as reimpleme +\hich\af4\dbch\af31505\loch\f4 nted by us in Java. See Knight & Ruiz, IMA Journal of Numerical Analysis, 2012; section II.b.4 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 +\hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell, 2014. Normalization factors are scaled such that the sum of the entries in the normalized c +\hich\af4\dbch\af31505\loch\f4 ontact matrix is equal to the sum of the entries in the raw contact matrix. +\par +\par \hich\af4\dbch\af31505\loch\f4 +INTERKRnorm = normalization vector obtained using the matrix balancing procedure of Knight and Ruiz on the entire genome-wide contact matrix without intrachromosomal contact matrices (i.e. only interchromosomal contact matrices), as reimplemented by us in +\hich\af4\dbch\af31505\loch\f4 \hich\af4\dbch\af31505\loch\f4 Java. See Knight & Ruiz, IMA Journal of Numerical Analysis, 2012; section II.b.4 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +, Cell, 2014. Normalization factors are scaled such that the sum of the entries in the normalized contact matrix \hich\af4\dbch\af31505\loch\f4 is equal to the sum of the entries in the raw contact matrix. +\par +\par \hich\af4\dbch\af31505\loch\f4 VCnorm = normalization vector obtained by calculating coverages (row-sums of the intrachromosomal contact matrix) for each locus as performed in Lieberman-Aiden, van Berkum, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 See Lieberma\hich\af4\dbch\af31505\loch\f4 n-Aiden, van Berkum, }{\rtlch\fcs1 \af4\afs24 +\ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Science 2009; section II.b.1 of the Extended Experimental Procedures of Rao, Huntley, } +{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +, Cell, 2014. Note that these values are not the reciprocals of the row-sums as written in section II.b.1 of the Extended Experimental Pr\hich\af4\dbch\af31505\loch\f4 ocedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +, Cell 2014 but rather are proportional to the row sums themselves, hence why one must divide the raw observed matrix entries by the normalization factors rather than multiplying. Normalization factors are scaled such that th +\hich\af4\dbch\af31505\loch\f4 e sum of the entries in the normalized contact matrix is equal to the sum of the entries in the raw contact matrix. +\par +\par \hich\af4\dbch\af31505\loch\f4 GWVCnorm = normalization vector obtained by calculating genome-wide coverages (row-sums of the genome-wide contact matrix, i.e. both intra-\hich\af4\dbch\af31505\loch\f4 + and inter-chromosomal contact matrices) for each locus as performed in Lieberman-Aiden, van Berkum, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 See Lieberman-Aiden, van Berkum, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\hich\af4\dbch\af31505\loch\f4 , Science 2009; section II.b.1 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell, 2014. Not\hich\af4\dbch\af31505\loch\f4 e that these values are not the reciprocals of the row-sums as written in section II.b.1 of the Extended Experimental Procedures of Rao, Huntley, }{ +\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +, Cell 2014 but rather are proportional to the row sums themselves, hence why one must divide the raw obs\hich\af4\dbch\af31505\loch\f4 +erved matrix entries by the normalization factors rather than multiplying. Normalization factors are scaled such that the sum of the entries in the normalized contact matrix is equal to the sum of the entries in the raw contact matrix. +\par +\par \hich\af4\dbch\af31505\loch\f4 INTERVCnorm = norma\hich\af4\dbch\af31505\loch\f4 +lization vector obtained by calculating interchromosomal coverages (row-sums across interchromosomal contact matrices) for each locus as performed in Lieberman-Aiden, van Berkum, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 +\hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 See Lieberman-Aiden, van Berkum, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 +\hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Science 2009; section II.b.1 o\hich\af4\dbch\af31505\loch\f4 f the Extended Experimental Procedures of Rao, Huntley, }{ +\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +, Cell, 2014. Note that these values are not the reciprocals of the row-sums as written in section II.b.1 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 +\hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell 2014 but rather are \hich\af4\dbch\af31505\loch\f4 +proportional to the row sums themselves, hence why one must divide the raw observed matrix entries by the normalization factors rather than multiplying. Normalization factors are scaled such that the sum of the entries in the normalized contact matrix is +\hich\af4\dbch\af31505\loch\f4 e\hich\af4\dbch\af31505\loch\f4 qual to the sum of the entries in the raw contact matrix. +\par +\par \hich\af4\dbch\af31505\loch\f4 SQRTVCnorm = normalization vector obtained by taking the square root of the VCnorm vector. See section II.b.1 of the Extended Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Cell, 2014. +\par +\par \hich\af4\dbch\af31505\loch\f4 RAWexpecte\hich\af4\dbch\af31505\loch\f4 d = a genome-wide model of interaction probability as a function of 1-dimensional genomic distance as introduced in Lieberman-Aiden, van Berkum, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 and refined by us. See Lieberman-Aiden, van Berkum, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 +\f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 , Science 2009; section II.c.1 of the Extended \hich\af4\dbch\af31505\loch\f4 +Experimental Procedures of Rao, Huntley, }{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 et al.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 \hich\af4\dbch\af31505\loch\f4 +, Cell, 2014. Note that while the expected vector is calculated by taking averages over all matrix entries at a fixed distance genome-wide, the vectors are independently scaled for each chromosome such that the\hich\af4\dbch\af31505\loch\f4 + sum of the entries for a given intrachromosomal expected matrix is equal to the sum of the entries for the in}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 \hich\af4\dbch\af31505\loch\f4 tr\hich\af4\dbch\af31505\loch\f4 +achromosomal observed matrix.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 KRexpected = the same model of interaction probability as a function of 1-dimensional genomic distance as RAWexp\hich\af4\dbch\af31505\loch\f4 +ected except calculated from the KR normalized contact matrix. Note that while the expected vector is calculated by taking averages over all matrix entries at a fixed distance genome-wide, the vectors are independently scaled for each chromosome such that +\hich\af4\dbch\af31505\loch\f4 \hich\af4\dbch\af31505\loch\f4 the sum of the entries for a given intrachromosomal expected matrix is equal to the sum of the entries for the in}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 +\hich\af4\dbch\af31505\loch\f4 trachromosomal observed matrix.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 VCexpected = the same model of interaction probability as a function of 1-dimensional genomic distance as RAW\hich\af4\dbch\af31505\loch\f4 +expected except calculated from the VC normalized contact matrix. Note that while the expected vector is calculated by taking averages over all matrix entries at a fixed distance genome-wide, the vectors are independently scaled for each chromosome such t +\hich\af4\dbch\af31505\loch\f4 h\hich\af4\dbch\af31505\loch\f4 at the sum of the entries for a given intrachromosomal expected matrix is equal to the sum of the entries for the in}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 +\hich\af4\dbch\af31505\loch\f4 trachromosomal observed matrix.}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid9332599 +\par +\par \hich\af4\dbch\af31505\loch\f4 SQRTVCexpected = the same model of interaction probability as a function of 1-dimensional genomic distance\hich\af4\dbch\af31505\loch\f4 + as RAWexpected except calculated from the SQRTVC normalized contact matrix. Note that while the expected vector is calculated by taking averages over all matrix entries at a fixed distance genome-wide, the vectors are independently scaled for each chromo +\hich\af4\dbch\af31505\loch\f4 s\hich\af4\dbch\af31505\loch\f4 ome such that the sum of the entries for a given intrachromosomal expected matrix is equal to the sum of the entries for the in}{\rtlch\fcs1 \af4\afs24 \ltrch\fcs0 \f4\fs24\insrsid14188250 +\hich\af4\dbch\af31505\loch\f4 trachromosomal observed matrix.}{\rtlch\fcs1 \af41\afs20 \ltrch\fcs0 \f41\fs20\insrsid9332599 +\par }{\*\themedata 504b030414000600080000002100e9de0fbfff0000001c020000130000005b436f6e74656e745f54797065735d2e786d6cac91cb4ec3301045f748fc83e52d4a +9cb2400825e982c78ec7a27cc0c8992416c9d8b2a755fbf74cd25442a820166c2cd933f79e3be372bd1f07b5c3989ca74aaff2422b24eb1b475da5df374fd9ad +5689811a183c61a50f98f4babebc2837878049899a52a57be670674cb23d8e90721f90a4d2fa3802cb35762680fd800ecd7551dc18eb899138e3c943d7e503b6 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b/3D/H1_MicroC/4DNFI2TK7L2F.hic new file mode 100644 index 0000000000000000000000000000000000000000..bc747dddaaa8ccbb9f5bdcc35ec11bef2ab3acec --- /dev/null +++ b/3D/H1_MicroC/4DNFI2TK7L2F.hic @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:618da62ad73e647fd56929a41e15070f62f5f1c40199e3a25d87f9d7aed585df +size 11037871316 diff --git a/3D/HiCDCPlus.R b/3D/HiCDCPlus.R new file mode 100644 index 0000000000000000000000000000000000000000..0dfe58e364e8cf34c4bdada267908f7d25868e26 --- /dev/null +++ b/3D/HiCDCPlus.R @@ -0,0 +1,108 @@ +# if (!requireNamespace("BiocManager", quietly = TRUE)) +# install.packages("BiocManager") +# +# BiocManager::install("HiCDCPlus") +# BiocManager::install("BSgenome.Hsapiens.UCSC.hg19") + + +library(HiCDCPlus) +library(BSgenome.Hsapiens.UCSC.hg19) + +# outdir <- "data/3D/K562_HiC/" +# hicfile_path <- paste0(outdir, "GSE63525_K562_combined_30.hic") +outdir <- "data/3D/GM12878_HiC/" +hicfile_path <- paste0(outdir, "GSE63525_GM12878_insitu_primary_30.hic") + + +process_chromosome <- function(chr) { + cat("Processing chromosome:", chr, "\n") + + feature_path <- paste0(outdir, "hg19_5kb_GATC_", chr) + + construct_features(output_path=feature_path, + gen="Hsapiens",gen_ver="hg19", + sig="GATC", + binsize=5000, + chrs=c(chr), + ) + # generated file under hg19_5kb_GATC_bintolen.txt.gz + + # generate gi_list instance + feature_output <- paste0(feature_path, "_bintolen.txt.gz") + + gi_list<-generate_bintolen_gi_list(bintolen_path=feature_output) + # add .hic counts + gi_list<-add_hic_counts(gi_list,hic_path = hicfile_path) + # expand features for modeling + gi_list<-expand_1D_features(gi_list) + + # run HiC-DC+ + set.seed(1010) #HiC-DC downsamples rows for modeling + gi_list<-HiCDCPlus_parallel(gi_list,ncore=2) + + cat("gi list length:", length(gi_list), "\n") + + + # select FDR < 0.1 + alpha <- 0.1 + + significant_interactions <- list() + + # 遍历 gi_list 中的每个 GInteractions 对象 + gi_list_names <- names(gi_list) + for (i in seq_along(gi_list)) { + name <- gi_list_names[i] + # 提取当前 GInteractions 对象 + gi <- gi_list[[i]] + metadata_columns <- mcols(gi) + qvalues <- metadata_columns$qvalue + significant_interaction <- gi[qvalues <= alpha, ] + + significant_interactions[[i]] <- significant_interaction + names(significant_interactions) <- name + } + + + # save file + # save_name = paste0(outdir,'GSE63525_K562_HiC30_FDR_1_', chr) + save_name = paste0(outdir,'GSE63525_GM12878_HiC30_FDR_1_', chr) + hicdc2hic(significant_interactions, + hicfile=paste0(save_name, '.hic'), + mode='normcounts', + gen_ver='hg19' + ) + gi_list_write(significant_interactions,fname=paste0(save_name, '.txt.gz')) + +} + + +chromosomes <- c("chr1", "chr2", "chr3", "chr4", "chr5", "chr6", "chr7", "chr8", "chr9", "chr10", + "chr11", "chr12", "chr13", "chr14", "chr15", "chr16", "chr17", "chr18", "chr19", "chr20", + "chr21", "chr22", "chrX") + +# Process each chromosome +for (chr in chromosomes) { + process_chromosome(chr) +} + + + +# # test +# library(InteractionSet) +# +# # 提取第一个 GInteractions 对象 +# gi <- gi_list[[1]] +# +# # 提取元数据列 +# metadata_columns <- mcols(gi) +# +# # 查看 qvalue 和 pvalue 列 +# qvalues <- metadata_columns$qvalue +# pvalues <- metadata_columns$pvalue +# +# # 检查 qvalue 和 pvalue 列的唯一值 +# unique_qvalues <- unique(qvalues) +# unique_pvalues <- unique(pvalues) +# +# num_qvalues_less_than_0.1 <- sum(qvalues < 0.1, na.rm = TRUE) + diff --git a/3D/K562_H3K27ac_HiChIP/.DS_Store b/3D/K562_H3K27ac_HiChIP/.DS_Store new file mode 100644 index 0000000000000000000000000000000000000000..5008ddfcf53c02e82d7eee2e57c38e5672ef89f6 Binary files /dev/null and b/3D/K562_H3K27ac_HiChIP/.DS_Store differ diff --git a/3D/K562_H3K27ac_HiChIP/GSE101498_K562_HiChIP_H3K27ac_HiC_output_files_from_Juicebox.tar.gz b/3D/K562_H3K27ac_HiChIP/GSE101498_K562_HiChIP_H3K27ac_HiC_output_files_from_Juicebox.tar.gz new file mode 100644 index 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