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Parameswaran, S.

Publications and source records attributed to Parameswaran, S..

2 recordsLinked to original sources

Featherweight long read alignment using partitioned reference indexes

The advent of nanopore sequencing has realised portable genomic research and applications. However, state of the art long read aligners and large reference genomes are not compatible with most mobile computing devices due to their high memory requirements. We show how memory requirements can be reduced through parameter optimization and reference genome partitioning, but highlight the associated limitations and caveats of these approaches. We then demonstrate how these issues can be overcome through an appropriate merging technique. We extend the Minimap2 aligner and demonstrate that long read alignment to the human genome can be performed on a system with 2GB RAM with negligible impact on accuracy.

bioinformatics

Expression-based analyses indicate a central role for hypoxia in driving tumor plasticity through microenvironment remodeling and chromosomal instability

Can transcriptomic alterations drive the evolution of tumors? We rationalize that expressional changes found in all patients arise earlier in tumor development compared to alterations that occur only in limited subsets of patients. Our analyses of non-mutated genes from the non-amplified regions of the genome of 158 triple negative breast cancer (TNBC) cases identified 219 exclusively expression-altered (EEA) genes that may play important role in TNBC. Phylogenetic analyses of these genes predict a \"punctuated burst\" of multiple gene up-regulation events occurring at early stages of tumor development, followed by minimal subsequent changes later in tumor progression. Remarkably, this punctuated burst of expressional changes is instigated by hypoxia-related molecular events, predominantly in two groups of genes that control chromosomal instability (CIN) and remodel tumor microenvironment (TME). We conclude that alterations in the transcriptome are not stochastic and that early stage hypoxia induces CIN and TME remodeling to permit further tumor evolution.

cancer biology