The exceptional genomic word symmetry along DNA sequences

Abstract

BackgroundThe second Chargaff’s parity rule and its extensions are recognized as universal phenomena in DNA sequences. However, parity of the frequencies of reverse complementary oligonucleotides could be a mere consequence of the single nucleotide parity rule, if nucleotide independence is assumed. Exceptional symmetry (symmetry beyond that expected under an independent nucleotide assumption) was proposed previously as a meaningful measure of the extension of the second parity rule to oligonucleotides. The global exceptional symmetry was detected in long and short genomes.ResultsTo explore the exceptional genomic word symmetry along the genome sequences, we propose a sliding window method to extract the values of exceptional symmetry (for all words or by word groups). We compare the exceptional symmetry effect size distribution in all human chromosomes against control scenarios (positive and negative controls), testing the differences and performing a residual analysis. We explore local exceptional symmetry in equivalent composition word groups, and find that the behaviour of the local exceptional symmetry depends on the word group.ConclusionsWe conclude that the exceptional symmetry is a local phenomenon in genome sequences, with distinct characteristics along the sequence of each chromosome. The local exceptional symmetry along the genomic sequences shows outlying segments, and those segments have high biological annotation density.

A pathways-based prediction model for classifying breast cancer subtypes

“…To analyze dynamic changes in functional levels with increasing degrees of malignancy in the four subtypes, we applied the sliding window approach [ 13 ] to integrate pathway scores for the four subtypes (Figure 9 ). The LOESS fitting algorithm [ 14 ] was used to smooth the data.…”

“…We evaluated dynamic pathway alterations among the different subtypes using the sliding window [ 13 ] and LOESS fitting [ 14 ] methods. The classic functional and disease pathways identified in this study showed functional level differences among the four subtypes, exhibiting primarily linear changes correlated with degree of malignancy.…”

“…The alteration score of the variation pathway was calculated for each sample. To filter out interfering noise signals while observing dynamic changes in the pathway during transition between two subtypes, the score of each pathway was integrated using the sliding window approach [ 13 ]. From the starting end, every 20 samples were integrated as a window, with 10 samples overlapping between adjacent windows.…”

“…In addition, functional enrichment analysis identified six biological pathways associated with these 136 core genes. We analyzed gene co-expression patterns to infer associated pathways and to evaluate dynamic pathway alterations in the different subtypes based on the sliding window [ 13 ] and loess fitting [ 14 ] methods. Ultimately, we used the six pathways as features to build a support vector machine (SVM) model.…”

Evaluation of the Persistence of Higher-Order Strand Symmetry in Genomic Sequences by Novel Word Symmetry Distance Analysis

“…Strand symmetry, also called the second parity rule, exists in almost all modern cellular genomes (genomes in living organisms nowadays on Earth). It is the phenomenon in which the numbers of occurrence of individual nucleotides and oligonucleotides (words) match well and exclusively with those of their respective reverse complements (complementary words) in each genomic DNA strand of sufficient length (e.g., for tetranucleotide GTCA vs. TGAC; for review see Baisnée et al, 2002 ; Forsdyke and Bell, 2004 ; Albrecht-Buehler, 2006 ; Zhang and Huang, 2010 ; Afreixo et al, 2016 ; Shporer et al, 2016 ). As an important feature of genome compositional structures, strand symmetry may persist for higher-order oligonucleotides, while the degree of symmetry decreases with increasing order (see Zhang and Huang, 2008 for example).…”