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    36 <body lang=EN-US>
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    37 
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    38 <div class=WordSection1>
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    39 
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    40 <p class=MsoNormalCxSpFirst style='text-align:justify'><b><span lang=EN-GB
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    41 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Info
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    42 table</span></b></p>
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    43 
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    44 <p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
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    45 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>This
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    46 table contains information on different characteristics of SHM. For all
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    47 characteristics information can be found for all sequences or only sequences of
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    48 a certain (sub)class. All results are based on the sequences that passed the filter
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    49 settings chosen on the start page of the SHM & CSR pipeline and only
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    50 include details on the analysed region as determined by the setting of the
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    51 sequence starts at filter. All data in this table can be downloaded via the
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    52 “downloads” tab.</span></p>
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    53 
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    54 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
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    55 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Mutation
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    56 frequency:</span></u></p>
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    57 
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    58 <p class=MsoNormalCxSpMiddle style='text-align:justify'><a name="OLE_LINK83"></a><a
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    59 name="OLE_LINK82"></a><a name="OLE_LINK81"><span lang=EN-GB style='font-size:
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    60 12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These values
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    61 give information on the level of SHM. </span></a><a name="OLE_LINK22"></a><a
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    62 name="OLE_LINK21"></a><a name="OLE_LINK20"><span lang=EN-GB style='font-size:
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    63 12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>More information
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    64 on the values found in healthy individuals of different ages can be found in </span></a><a
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    65 name="OLE_LINK15"></a><a name="OLE_LINK14"></a><a name="OLE_LINK13"><span
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    66 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>IJspeert
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    67 and van Schouwenburg et al, PMID: 27799928</span></a></p>
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    68 
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    69 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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    70 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Number
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    71 of mutations:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:
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    72 115%;font-family:"Times New Roman","serif"'> Shows the number of total
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    73 mutations / the number of sequenced bases (the % of mutated bases).</span></p>
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    74 
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    75 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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    76 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Median
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    77 number of mutations:</span></i><span lang=EN-GB style='font-size:12.0pt;
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    78 line-height:115%;font-family:"Times New Roman","serif"'> Shows the median % of
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    79 SHM of all sequences.</span></p>
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    80 
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    81 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
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    82 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Patterns
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    83 of SHM:</span></u></p>
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    84 
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    85 <p class=MsoNormalCxSpMiddle style='text-align:justify'><a name="OLE_LINK72"></a><a
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    86 name="OLE_LINK71"></a><a name="OLE_LINK70"><span lang=EN-GB style='font-size:
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    87 12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These values
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    88 give insights into the targeting and patterns of SHM. These values can give
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    89 insight into the repair pathways used to repair the U:G mismatches introduced
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    90 by AID. </span></a><a name="OLE_LINK40"></a><a name="OLE_LINK39"></a><a
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    91 name="OLE_LINK38"></a><a name="OLE_LINK60"><span lang=EN-GB style='font-size:
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    92 12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>More information
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    93 on the values found in healthy individuals of different ages can be found in
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    94 IJspeert and van Schouwenburg et al, PMID: 27799928</span></a></p>
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    95 
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    96 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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    97 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Transitions:</span></i><span
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    98 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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    99 Shows the number of transition mutations / the number of total mutations (the
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   100 percentage of mutations that are transitions). Transition mutations are C>T,
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   101 T>C, A>G, G>A. </span></p>
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   102 
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   103 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   104 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Transversions:</span></i><span
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   105 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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   106 Shows the number of transversion mutations / the number of total mutations (the
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   107 percentage of mutations that are transitions). Transversion mutations are
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   108 C>A, C>G, T>A, T>G, A>T, A>C, G>T, G>C.</span></p>
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   109 
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   110 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   111 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Transitions
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   112 at GC:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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   113 font-family:"Times New Roman","serif"'> <a name="OLE_LINK2"></a><a
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   114 name="OLE_LINK1">Shows the number of transitions at GC locations (C>T,
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   115 G>A) / the total number of mutations at GC locations (the percentage of
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   116 mutations at GC locations that are transitions).</a></span></p>
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   117 
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   118 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   119 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Targeting
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   120 of GC:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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   121 font-family:"Times New Roman","serif"'> <a name="OLE_LINK7"></a><a
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   122 name="OLE_LINK6"></a><a name="OLE_LINK3">Shows the number of mutations at GC
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   123 locations / the total number of mutations (the percentage of total mutations
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   124 that are at GC locations).</a> </span></p>
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   125 
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   126 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   127 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Transitions
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   128 at AT:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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   129 font-family:"Times New Roman","serif"'> Shows the number of transitions at AT
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   130 locations (T>C, A>G) / the total number of mutations at AT locations (the
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   131 percentage of mutations at AT locations that are transitions).</span></p>
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   132 
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   133 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   134 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Targeting
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   135 of AT:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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   136 font-family:"Times New Roman","serif"'> Shows the number of mutations at AT
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   137 locations / the total number of mutations (the percentage of total mutations
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   138 that are at AT locations).</span></p>
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   139 
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   140 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   141 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>RGYW:</span></i><span
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   142 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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   143 <a name="OLE_LINK28"></a><a name="OLE_LINK27"></a><a name="OLE_LINK26">Shows
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   144 the number of mutations that are in a RGYW motive / The number of total mutations
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   145 (the percentage of mutations that are in a RGYW motive). </a><a
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   146 name="OLE_LINK62"></a><a name="OLE_LINK61">RGYW motives are known to be
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   147 preferentially targeted by AID </a></span><span lang=EN-GB style='font-size:
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   148 12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(R=Purine,
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   149 Y=pyrimidine, W = A or T).</span></p>
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   150 
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   151 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   152 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>WRCY:</span></i><span
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   153 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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   154 <a name="OLE_LINK34"></a><a name="OLE_LINK33">Shows the number of mutations
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   155 that are in a </a><a name="OLE_LINK32"></a><a name="OLE_LINK31"></a><a
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   156 name="OLE_LINK30"></a><a name="OLE_LINK29">WRCY</a> motive / The number of
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   157 total mutations (the percentage of mutations that are in a WRCY motive). WRCY
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   158 motives are known to be preferentially targeted by AID </span><span lang=EN-GB
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   159 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(R=Purine,
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   160 Y=pyrimidine, W = A or T).</span></p>
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   161 
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   162 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   163 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>WA:</span></i><span
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   164 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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   165 <a name="OLE_LINK37"></a><a name="OLE_LINK36"></a><a name="OLE_LINK35">Shows
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   166 the number of mutations that are in a WA motive / The number of total mutations
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   167 (the percentage of mutations that are in a WA motive). It is described that
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   168 polymerase eta preferentially makes errors at WA motives </a></span><span
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   169 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(W
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   170 = A or T).</span></p>
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   171 
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   172 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   173 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>TW:</span></i><span
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   174 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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   175 Shows the number of mutations that are in a TW motive / The number of total mutations
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   176 (the percentage of mutations that are in a TW motive). It is described that
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   177 polymerase eta preferentially makes errors at TW motives </span><span
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   178 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(W
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   179 = A or T).</span></p>
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   180 
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   181 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
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   182 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Antigen
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   183 selection:</span></u></p>
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   184 
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   185 <p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
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   186 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These
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   187 values give insight into antigen selection. It has been described that during
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   188 antigen selection, there is selection against replacement mutations in the FR
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   189 regions as these can cause instability of the B-cell receptor. In contrast
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   190 replacement mutations in the CDR regions are important for changing the
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   191 affinity of the B-cell receptor and therefore there is selection for this type
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   192 of mutations. Silent mutations do not alter the amino acid sequence and
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   193 therefore do not play a role in selection. More information on the values found
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   194 in healthy individuals of different ages can be found in IJspeert and van
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   195 Schouwenburg et al, PMID: 27799928</span></p>
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   196 
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   197 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   198 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>FR
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   199 R/S:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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   200 font-family:"Times New Roman","serif"'> <a name="OLE_LINK43"></a><a
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   201 name="OLE_LINK42"></a><a name="OLE_LINK41">Shows the number of replacement
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   202 mutations in the FR regions / The number of silent mutations in the FR regions
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   203 (the number of replacement mutations in the FR regions divided by the number of
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   204 silent mutations in the FR regions)</a></span></p>
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   205 
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   206 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   207 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>CDR
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   208 R/S:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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   209 font-family:"Times New Roman","serif"'> Shows the number of replacement
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   210 mutations in the CDR regions / The number of silent mutations in the CDR
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   211 regions (the number of replacement mutations in the CDR regions divided by the
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   212 number of silent mutations in the CDR regions)</span></p>
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   213 
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   214 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
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   215 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Number
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   216 of sequences nucleotides:</span></u></p>
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   217 
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   218 <p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
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   219 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These
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   220 values give information on the number of sequenced nucleotides.</span></p>
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   221 
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   222 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   223 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Nt
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   224 in FR:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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   225 font-family:"Times New Roman","serif"'> <a name="OLE_LINK46"></a><a
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   226 name="OLE_LINK45"></a><a name="OLE_LINK44">Shows the number of sequences bases
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   227 that are located in the FR regions / The total number of sequenced bases (the
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   228 percentage of sequenced bases that are present in the FR regions).</a></span></p>
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   229 
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   230 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   231 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Nt
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   232 in CDR:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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   233 font-family:"Times New Roman","serif"'> Shows the number of sequenced bases
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   234 that are located in the CDR regions / <a name="OLE_LINK48"></a><a
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   235 name="OLE_LINK47">The total number of sequenced bases (the percentage of
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   236 sequenced bases that are present in the CDR regions).</a></span></p>
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   237 
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   238 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   239 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>A:
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   240 </span></i><a name="OLE_LINK51"></a><a name="OLE_LINK50"></a><a
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   241 name="OLE_LINK49"><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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   242 font-family:"Times New Roman","serif"'>Shows the total number of sequenced
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   243 adenines / The total number of sequenced bases (the percentage of sequenced
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   244 bases that were adenines).</span></a></p>
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   245 
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   246 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   247 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>C:
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   248 </span></i><a name="OLE_LINK53"></a><a name="OLE_LINK52"><span lang=EN-GB
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   249 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Shows
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   250 the total number of sequenced cytosines / The total number of sequenced bases
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   251 (the percentage of sequenced bases that were cytosines).</span></a></p>
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   252 
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   253 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   254 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>T:
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   255 </span></i><a name="OLE_LINK57"></a><a name="OLE_LINK56"><span lang=EN-GB
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   256 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Shows
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   257 the total number of sequenced </span></a><a name="OLE_LINK55"></a><a
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   258 name="OLE_LINK54"><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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   259 font-family:"Times New Roman","serif"'>thymines</span></a><span lang=EN-GB
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   260 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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   261 / The total number of sequenced bases (the percentage of sequenced bases that
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   262 were thymines).</span></p>
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   263 
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   264 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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   265 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>G:
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   266 </span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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   267 font-family:"Times New Roman","serif"'>Shows the total number of sequenced <a
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   268 name="OLE_LINK59"></a><a name="OLE_LINK58">guanine</a>s / The total number of
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   269 sequenced bases (the percentage of sequenced bases that were guanines).</span></p>
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   270 
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   271 <p class=MsoNormalCxSpMiddle style='text-align:justify'><a name="OLE_LINK69"><b><span
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   272 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Graphs</span></b></a></p>
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   273 
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   274 <p class=MsoNormalCxSpMiddle style='text-align:justify'><a name="OLE_LINK75"></a><a
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   275 name="OLE_LINK74"></a><a name="OLE_LINK73"><span lang=EN-GB style='font-size:
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   276 12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These graphs visualize
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   277 information on the patterns and targeting of SHM and thereby give information
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   278 into the repair pathways used to repair the U:G mismatches introduced by AID. The
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   279 data represented in these graphs can be downloaded in the download tab. More
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   280 information on the values found in healthy individuals of different ages can be
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   281 found in IJspeert and van Schouwenburg et al, PMID: 27799928</span></a><span
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   282 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>.
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   283 <a name="OLE_LINK85"></a><a name="OLE_LINK84"></a></span></p>
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   284 
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   285 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
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   286 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Percentage
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   287 of mutations in AID and pol eta motives</span></u></p>
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   288 
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   289 <p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
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   290 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Visualizes
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   291 <a name="OLE_LINK80"></a><a name="OLE_LINK79"></a><a name="OLE_LINK78">for each
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   292 (sub)class </a>the percentage of mutations that are present in AID (RGYW or
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   293 WRCY) or polymerase eta motives (WA or TW) in the different subclasses </span><span
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   294 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(R=Purine,
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   295 Y=pyrimidine, W = A or T).</span></p>
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   296 
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   297 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=NL
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   298 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Relative
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   299 mutation patterns</span></u></p>
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   300 
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   301 <p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
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   302 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Visualizes
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   303 for each (sub)class the distribution of mutations between mutations at AT
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   304 locations and transitions or transversions at GC locations. </span></p>
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   305 
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   306 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=NL
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   307 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Absolute
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   308 mutation patterns</span></u></p>
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   309 
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   310 <p class=MsoNormalCxSpLast style='text-align:justify'><span lang=EN-GB
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   311 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Visualized
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   312 for each (sub)class the percentage of sequenced AT and GC bases that are
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   313 mutated. The mutations at GC bases are divided into transition and transversion
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   314 mutations<a name="OLE_LINK77"></a><a name="OLE_LINK76">. </a></span></p>
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   315 
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   316 <p class=MsoNormal><span lang=NL style='font-size:12.0pt;line-height:115%;
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   317 font-family:"Times New Roman","serif"'>Hanna IJspeert, Pauline A. van
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   318 Schouwenburg, David van Zessen, Ingrid Pico-Knijnenburg, Gertjan J. Driessen,
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   319 Andrew P. Stubbs, and Mirjam van der Burg (2016). </span><span
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   320 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Evaluation
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   321 of the Antigen-Experienced B-Cell Receptor Repertoire in Healthy Children and
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   322 Adults. In <i>Frontiers in Immunolog, 7, pp. e410-410. </i>[<a
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   323 href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066086/"><span
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   324 style='color:windowtext'>doi:10.3389/fimmu.2016.00410</span></a>][<a
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   325 href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066086/"><span
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   326 style='color:windowtext'>Link</span></a>]</span></p>
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   327 
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   328 </div>
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   329 
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   330 </body>
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   331 
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   332 </html>
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