Policy Document
 
DATABASES
SUBMISSIONS
NEWS

 

Site requirements

 
previous | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | Figures | next

Building up the eBURST diagram

The original BURST algorithm identifies the primary founder as the ST with the largest number of SLVs. Those STs that are SLVs of the predicted primary founder are assigned to the primary founder and the new ST that has the greatest number of previously unassigned SLVs is identified. The iterative process of identifying the new ST with the greatest number of previously unassigned SLVs continues until all of the STs that have multiple unassigned SLVs (subgroup founders) have been identified. DLVs of the primary founder and of the subgroup founders are then identified in a similar iterative manner. The original BURST displayed the primary founder and the subgroup founders, and their SLVs and DLVs, but did not attempt to link all of these clusters of STs together.

In eBURST, the default group definition results in all STs being connected as a single clonal complex and eBURST makes these links. However, if the primary founder and subgroup founders, and their SLVs and DLVs, are assigned as described above for the original BURST algorithm, there can be problems in achieving a fully linked diagram without introducing ad hoc linking rules. In order to circumvent this problem, eBURST produces an initial approximation of the above arrangement of STs, which ensures that all STs in the group are linked, and then optimises the arrangement of STs to produce the final eBURST diagram.

The procedure is as follows. The ST that has the greatest number of SLVs is assigned as the primary founder and is positioned centrally with radial links to all of its SLVs. Having assigned all of the SLVs of the primary founder, the SLVs of each of these SLVs are identified (ignoring any STs that have already been assigned to the primary founder) and linked, and this iterative procedure of linking previously unassigned SLVs carries on outwards from the SLVs, to the DLVs and then to the TLVs, until all SLV links have been made.

Optimisation of the initial arrangement of STs is then carried out. The optimisation method looks at each ST (excepting the primary founder and its SLVs, which are unambiguously assigned) and searches for a better positioning of STs that maximises the numbers of SLVs associated with subgroup founders. Optimisation takes account of the simple model of clonal expansion that underpins BURST where some STs within a clonal complex may have increased in frequency and diversified to produce subgroups. It attempts to identify the most likely pattern of subgroups by searching for those subgroup founders that have the greatest numbers of linked SLVs.

Figure 2


An illustrative example is shown in Figure 2. The initial procedure identifies ST1 as the ST with the greatest number of SLVs (the primary founder) and links ST1 to its seven SLVs. It then assigns the SLVs of each of these seven SLVs, and identifies ST2 as a SLV of ST17 and links it. Progressing further outwards, the four descendent SLVs of ST2 are identified and linked, and the process continues outwards and links the four descendent SLVs of ST3. This initial assignment of SLVs from the primary founder outwards results in STs that are SLVs of more than one ST being preferentially assigned to the more centrally positioned ST (ST2 in Figure 2).

In the example shown in Figure 2, optimisation identifies ST10 and ST12 as SLVs of ST3 as well as of ST2. The optimisation procedure re-assigns STs to maximise the numbers of SLVs associated with ST3 as this subgroup founder has more SLVs than ST2 and thus is a more likely subgroup founder. ST2 and ST3 each start with four SLVs and after optimisation ST3 ends up with six linked SLVs (STs 10, 12, 13, 14, 15 and 16) and ST2 with two linked SLVs (STs 3 and 11). Optimisation re-organises the arrangement of STs to maximise the numbers of SLVs associated with subgroup founders, closely approximating the sub-groups produced by the original BURST algorithm, but providing complete linkage between all of the STs in the group.