fragments. Fragments to be joined must be co-linear and have the same age, as estimated using the percentage of identity with the TE reference sequence (20). In the ‘nest join’ version of the procedure, the inner TE sequence cover >95% of the region between the two fragments to be joined and be younger. TE sequences can also be split as a result of large non-TE sequence insertions. To account for this possibility, TE fragments that have the same age, are separated by an insert of <5 kb and align within 500 bp of each other on the TE reference sequence (Figure 1) are joined in a version of the ‘long join’ pro- cedure referred to as ‘simple join’. TE fragments already connected in a previous step by MATCHER are split if inner TE fragments are younger than outer joined fragments. Although the ‘long join’ pro- cedure outperforms MATCHER, which relies on dynamic programming and a scoring scheme that are ill adapted for extreme situations, it did produce only few ‘simple join’ and no ‘nest join’. Indeed, many ‘long join’ were denied because fragments are too dissimilar in age (>2% differ- ence in age) or too far apart (>100 kb). Results are summarized in Supplementary Table S5. Assigning conﬁdence scores to TE sequence models The pipeline provides TE sequence models composed of four lines of evidence, one for each TE reference sequence set. The longest evidence (maximum length) for each TE sequence model is recognized as ‘best evidence’ and is used to determine the precise genomic coordinates. A score is assigned to the model based on the origin of the best evidence supporting the model. Indeed, because small in- sertions, unrelated to the TE sequence, may be present in the genomic copies that were used for building the Figure 1. Schematic dot plot representation of ‘simple join’ conditions. Matching regions between genomic and TE reference sequence are rep- resented by diagonals. Note that these regions might be fragments already connected by MATCHER. X and Y indicate percentage of identity to the TE reference sequence. a and b refer to the length of non-matching DNA on the TE reference and genomic sequences, respectively. Nucleic Acids Research, 2011, Vol. 39, No. 16 6921 OptCoding, MaxSize and Opt TE reference sequence sets (7), evidence obtained with these different sets may not be all equally reliable. In fact, the coding constraint imposed on the OptCoding design makes this TE reference sequence set more reliable than Opt and MaxSize. A score of 3 (best) is attributed to models supported by at least RU or OptCoding, a score of 2 when support comes from Opt only and a score of 1 when support come from MaxSize alone. In cases where the longest evidence has a lower score than shorter evidence (>100 bp) and does not expand it by >50 bp, the higher score is assigned to the longest evidence. Satellites are comprised of highly embedded tandem re- peats, and the long-join procedure does not seem to work well when the TE reference sequence sets OptCoding, Opt or MaxSize are used. Indeed these TE-reference-sequence sets tend to merge many satellite units into one big unit. In contrast, RU tends to keep unit boundaries for tandem repeats. Satellites were thus annotated solely based on RU evidence and with no score attached. RU provides best evidence for the largest set 12 922 (40%) of annotated TE sequence models, followed by Opt 12 214 (38%), MaxSize 5758 (18%) and OptCoding 981 (4%). Of the 31 245 annotated TE models, 13 752 (44%) have a score of 3; 11 773 (37.7%) a score of 2 and 5720 (18.3%) a score of 1. In addition, 3342 sequences were annotated as satellites. Note that because of the stringent statistical threshold used to detect TE se- quences with high conﬁdence, some old TE insertions are likely missed, such as those proposed to be responsible for the epigenetic regulation of the imprinted gene FWA (21). DNA methylation analysis Single-nucleotide resolution DNA methylation data were used from Cokus et al. (5). DNA methylation analysis was carried out separately for CG, CHG and CHH sites (Supplementary Figure S6). Sites were considered as methylated if at least 10% of the reads (CG sites) or at least one read (CHG and CHH sites) were indicative of methylation. However, because CG methylation was found to be symmetrical, as expected, methylation status was copied to the opposite strand in cases of no or insuf- ﬁcient coverage for that strand. Although CHG sites are symmetrical, CHG methylation was found to depart sig- niﬁcantly from symmetry in a large number of cases, and thus methylation status of CHG sites was not copied to the opposite strand in cases of insufﬁcient coverage for one strand. Once the methylation status of all available sites was established, DNA methylation for TE sequences or any other annotated feature is computed as a fraction of methylated Cs to the total number of covered Cs, for each of the three types of sites. High-density tiling microarray datasets (22) were down- loaded from the Gene Expression Omnibus (GSE5974). Potentially cross-hybridizing probes were identiﬁed by aligning them on the genomic sequence with nucmer from the MUMmer v3 package (23) with parameters: –maxmatch –minmatch=10 –mincluster=50 –nosimplify. A total of 36 993 probes (out of 382 178) were removed from the analysis because they had multiple matches with