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<p class=MsoNormalCxSpFirst style='text-align:justify'><b><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Info
table</span></b></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>This
table contains information on different characteristics of SHM. For all
characteristics information can be found for all sequences or only sequences of
a certain (sub)class. All results are based on the sequences that passed the filter
settings chosen on the start page of the SHM &amp; CSR pipeline and only
include details on the analysed region as determined by the setting of the
sequence starts at filter. All data in this table can be downloaded via the
“downloads” tab.</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Mutation
frequency:</span></u></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><a name="OLE_LINK83"></a><a
name="OLE_LINK82"></a><a name="OLE_LINK81"><span lang=EN-GB style='font-size:
12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These values
give information on the level of SHM. </span></a><a name="OLE_LINK22"></a><a
name="OLE_LINK21"></a><a name="OLE_LINK20"><span lang=EN-GB style='font-size:
12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>More information
on the values found in healthy individuals of different ages can be found in </span></a><a
name="OLE_LINK15"></a><a name="OLE_LINK14"></a><a name="OLE_LINK13"><span
lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>IJspeert
and van Schouwenburg et al, PMID: 27799928</span></a></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Number
of mutations:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:
115%;font-family:"Times New Roman","serif"'> Shows the number of total
mutations / the number of sequenced bases (the % of mutated bases).</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Median
number of mutations:</span></i><span lang=EN-GB style='font-size:12.0pt;
line-height:115%;font-family:"Times New Roman","serif"'> Shows the median % of
SHM of all sequences.</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Patterns
of SHM:</span></u></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><a name="OLE_LINK72"></a><a
name="OLE_LINK71"></a><a name="OLE_LINK70"><span lang=EN-GB style='font-size:
12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These values
give insights into the targeting and patterns of SHM. These values can give
insight into the repair pathways used to repair the U:G mismatches introduced
by AID. </span></a><a name="OLE_LINK40"></a><a name="OLE_LINK39"></a><a
name="OLE_LINK38"></a><a name="OLE_LINK60"><span lang=EN-GB style='font-size:
12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>More information
on the values found in healthy individuals of different ages can be found in
IJspeert and van Schouwenburg et al, PMID: 27799928</span></a></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Transitions:</span></i><span
lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
Shows the number of transition mutations / the number of total mutations (the
percentage of mutations that are transitions). Transition mutations are C&gt;T,
T&gt;C, A&gt;G, G&gt;A. </span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Transversions:</span></i><span
lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
Shows the number of transversion mutations / the number of total mutations (the
percentage of mutations that are transitions). Transversion mutations are
C&gt;A, C&gt;G, T&gt;A, T&gt;G, A&gt;T, A&gt;C, G&gt;T, G&gt;C.</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Transitions
at GC:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
font-family:"Times New Roman","serif"'> <a name="OLE_LINK2"></a><a
name="OLE_LINK1">Shows the number of transitions at GC locations (C&gt;T,
G&gt;A) / the total number of mutations at GC locations (the percentage of
mutations at GC locations that are transitions).</a></span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Targeting
of GC:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
font-family:"Times New Roman","serif"'> <a name="OLE_LINK7"></a><a
name="OLE_LINK6"></a><a name="OLE_LINK3">Shows the number of mutations at GC
locations / the total number of mutations (the percentage of total mutations
that are at GC locations).</a> </span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Transitions
at AT:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
font-family:"Times New Roman","serif"'> Shows the number of transitions at AT
locations (T&gt;C, A&gt;G) / the total number of mutations at AT locations (the
percentage of mutations at AT locations that are transitions).</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Targeting
of AT:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
font-family:"Times New Roman","serif"'> Shows the number of mutations at AT
locations / the total number of mutations (the percentage of total mutations
that are at AT locations).</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>RGYW:</span></i><span
lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
<a name="OLE_LINK28"></a><a name="OLE_LINK27"></a><a name="OLE_LINK26">Shows
the number of mutations that are in a RGYW motive / The number of total mutations
(the percentage of mutations that are in a RGYW motive). </a><a
name="OLE_LINK62"></a><a name="OLE_LINK61">RGYW motives are known to be
preferentially targeted by AID </a></span><span lang=EN-GB style='font-size:
12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(R=Purine,
Y=pyrimidine, W = A or T).</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>WRCY:</span></i><span
lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
<a name="OLE_LINK34"></a><a name="OLE_LINK33">Shows the number of mutations
that are in a </a><a name="OLE_LINK32"></a><a name="OLE_LINK31"></a><a
name="OLE_LINK30"></a><a name="OLE_LINK29">WRCY</a> motive / The number of
total mutations (the percentage of mutations that are in a WRCY motive). WRCY
motives are known to be preferentially targeted by AID </span><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(R=Purine,
Y=pyrimidine, W = A or T).</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>WA:</span></i><span
lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
<a name="OLE_LINK37"></a><a name="OLE_LINK36"></a><a name="OLE_LINK35">Shows
the number of mutations that are in a WA motive / The number of total mutations
(the percentage of mutations that are in a WA motive). It is described that
polymerase eta preferentially makes errors at WA motives </a></span><span
lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(W
= A or T).</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>TW:</span></i><span
lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
Shows the number of mutations that are in a TW motive / The number of total mutations
(the percentage of mutations that are in a TW motive). It is described that
polymerase eta preferentially makes errors at TW motives </span><span
lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(W
= A or T).</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Antigen
selection:</span></u></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These
values give insight into antigen selection. It has been described that during
antigen selection, there is selection against replacement mutations in the FR
regions as these can cause instability of the B-cell receptor. In contrast
replacement mutations in the CDR regions are important for changing the
affinity of the B-cell receptor and therefore there is selection for this type
of mutations. Silent mutations do not alter the amino acid sequence and
therefore do not play a role in selection. More information on the values found
in healthy individuals of different ages can be found in IJspeert and van
Schouwenburg et al, PMID: 27799928</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>FR
R/S:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
font-family:"Times New Roman","serif"'> <a name="OLE_LINK43"></a><a
name="OLE_LINK42"></a><a name="OLE_LINK41">Shows the number of replacement
mutations in the FR regions / The number of silent mutations in the FR regions
(the number of replacement mutations in the FR regions divided by the number of
silent mutations in the FR regions)</a></span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>CDR
R/S:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
font-family:"Times New Roman","serif"'> Shows the number of replacement
mutations in the CDR regions / The number of silent mutations in the CDR
regions (the number of replacement mutations in the CDR regions divided by the
number of silent mutations in the CDR regions)</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Number
of sequences nucleotides:</span></u></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These
values give information on the number of sequenced nucleotides.</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Nt
in FR:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
font-family:"Times New Roman","serif"'> <a name="OLE_LINK46"></a><a
name="OLE_LINK45"></a><a name="OLE_LINK44">Shows the number of sequences bases
that are located in the FR regions / The total number of sequenced bases (the
percentage of sequenced bases that are present in the FR regions).</a></span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Nt
in CDR:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
font-family:"Times New Roman","serif"'> Shows the number of sequenced bases
that are located in the CDR regions / <a name="OLE_LINK48"></a><a
name="OLE_LINK47">The total number of sequenced bases (the percentage of
sequenced bases that are present in the CDR regions).</a></span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>A:
</span></i><a name="OLE_LINK51"></a><a name="OLE_LINK50"></a><a
name="OLE_LINK49"><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
font-family:"Times New Roman","serif"'>Shows the total number of sequenced
adenines / The total number of sequenced bases (the percentage of sequenced
bases that were adenines).</span></a></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>C:
</span></i><a name="OLE_LINK53"></a><a name="OLE_LINK52"><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Shows
the total number of sequenced cytosines / The total number of sequenced bases
(the percentage of sequenced bases that were cytosines).</span></a></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>T:
</span></i><a name="OLE_LINK57"></a><a name="OLE_LINK56"><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Shows
the total number of sequenced </span></a><a name="OLE_LINK55"></a><a
name="OLE_LINK54"><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
font-family:"Times New Roman","serif"'>thymines</span></a><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
/ The total number of sequenced bases (the percentage of sequenced bases that
were thymines).</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>G:
</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
font-family:"Times New Roman","serif"'>Shows the total number of sequenced <a
name="OLE_LINK59"></a><a name="OLE_LINK58">guanine</a>s / The total number of
sequenced bases (the percentage of sequenced bases that were guanines).</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><a name="OLE_LINK69"><b><span
lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Graphs</span></b></a></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><a name="OLE_LINK75"></a><a
name="OLE_LINK74"></a><a name="OLE_LINK73"><span lang=EN-GB style='font-size:
12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These graphs visualize
information on the patterns and targeting of SHM and thereby give information
into the repair pathways used to repair the U:G mismatches introduced by AID. The
data represented in these graphs can be downloaded in the download tab. More
information on the values found in healthy individuals of different ages can be
found in IJspeert and van Schouwenburg et al, PMID: 27799928</span></a><span
lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>.
<a name="OLE_LINK85"></a><a name="OLE_LINK84"></a></span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Percentage
of mutations in AID and pol eta motives</span></u></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Visualizes
<a name="OLE_LINK80"></a><a name="OLE_LINK79"></a><a name="OLE_LINK78">for each
(sub)class </a>the percentage of mutations that are present in AID (RGYW or
WRCY) or polymerase eta motives (WA or TW) in the different subclasses </span><span
lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(R=Purine,
Y=pyrimidine, W = A or T).</span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=NL
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Relative
mutation patterns</span></u></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Visualizes
for each (sub)class the distribution of mutations between mutations at AT
locations and transitions or transversions at GC locations. </span></p>

<p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=NL
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Absolute
mutation patterns</span></u></p>

<p class=MsoNormalCxSpLast style='text-align:justify'><span lang=EN-GB
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Visualized
for each (sub)class the percentage of sequenced AT and GC bases that are
mutated. The mutations at GC bases are divided into transition and transversion
mutations<a name="OLE_LINK77"></a><a name="OLE_LINK76">. </a></span></p>

<p class=MsoNormal><span lang=NL style='font-size:12.0pt;line-height:115%;
font-family:"Times New Roman","serif"'>Hanna IJspeert, Pauline A. van
Schouwenburg, David van Zessen, Ingrid Pico-Knijnenburg, Gertjan J. Driessen,
Andrew P. Stubbs, and Mirjam van der Burg (2016). </span><span
style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Evaluation
of the Antigen-Experienced B-Cell Receptor Repertoire in Healthy Children and
Adults. In <i>Frontiers in Immunolog, 7, pp. e410-410. </i>[<a
href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066086/"><span
style='color:windowtext'>doi:10.3389/fimmu.2016.00410</span></a>][<a
href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066086/"><span
style='color:windowtext'>Link</span></a>]</span></p>

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