Comparison of single-cell whole-genome amplification strategies, bioRxiv, 2018-10-16

Single-cell genomics is an alluring area that holds the potential to change the way we understand cell populations. Due to the small amount of DNA within a single cell, whole-genome amplification becomes a mandatory step in many single-cell applications. Unfortunately, single-cell whole-genome amplification (scWGA) strategies suffer from several technical biases that complicate the posterior interpretation of the data. Here we compared the performance of six different scWGA methods (GenomiPhi, REPLIg, TruePrime, Ampli1, MALBAC, and PicoPLEX) after amplifying and low-pass sequencing the complete genome of 230 healthytumoral human cells. Overall, REPLIg outperformed competing methods regarding DNA yield, amplicon size, amplification breadth, amplification uniformity –being the only method with a random amplification bias–, and false single-nucleotide variant calls. On the other hand, non-MDA methods, and in particular Ampli1, showed less allelic imbalance and ADO, more reliable copy-number profiles and less chimeric amplicons. While no single scWGA method showed optimal performance for every aspect, they clearly have distinct advantages. Our results provide a convenient guide for selecting a scWGA method depending on the question of interest while revealing relevant weaknesses that should be considered during the analysis and interpretation of single-cell sequencing data.

biorxiv genomics 100-200-users 2018

The whale shark genome reveals how genomic and physiological properties scale with body size, bioRxiv, 2018-10-14

AbstractThe endangered whale shark (Rhincodon typus) is the largest fish on Earth and is a long-lived member of the ancient Elasmobranchii clade. To characterize the relationship between genome features and biological traits, we sequenced and assembled the genome of the whale shark and compared its genomic and physiological features to those of 81 animals and yeast. We examined scaling relationships between body size, temperature, metabolic rates, and genomic features and found both general correlations across the animal kingdom and features specific to the whale shark genome. Among animals, increased lifespan is positively correlated to body size and metabolic rate. Several genomic features also significantly correlated with body size, including intron and gene length. Our large-scale comparative genomic analysis uncovered general features of metazoan genome architecture GC content and codon adaptation index are negatively correlated, and neural connectivity genes are longer than average genes in most genomes. Focusing on the whale shark genome, we identified multiple features that significantly correlate with lifespan. Among these were very long gene length, due to large introns highly enriched in repetitive elements such as CR1-like LINEs, and considerably longer neural genes of several types, including connectivity, activity, and neurodegeneration genes. The whale shark’s genome had an expansion of gene families related to fatty acid metabolism and neurogenesis, with the slowest evolutionary rate observed in vertebrates to date. Our comparative genomics approach uncovered multiple genetic features associated with body size, metabolic rate, and lifespan, and showed that the whale shark is a promising model for studies of neural architecture and lifespan.

biorxiv genomics 0-100-users 2018

 

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