Honors & Awards

  • Postdoctoral fellowship, Stanford Center for Computational, Evolutionary and Human Genomics (2015-2016)
  • PhD fellowship, Erasmus Mundus (2010-2013)

Professional Education

  • PhD, Institute Curie, University Pierre et Marie Curie, Computational Biology (2013)
  • MS, University of Pune, Bioinformatics (2008)

Stanford Advisors

All Publications

  • Identification of Ohnolog Genes Originating from Whole Genome Duplication in Early Vertebrates, Based on Synteny Comparison across Multiple Genomes PLOS COMPUTATIONAL BIOLOGY Singh, P. P., Arora, J., Isambert, H. 2015; 11 (7)


    Whole genome duplications (WGD) have now been firmly established in all major eukaryotic kingdoms. In particular, all vertebrates descend from two rounds of WGDs, that occurred in their jawless ancestor some 500 MY ago. Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation. Ohnologs, which amount to about 20 to 35% of genes in the human genome, have also been shown to be prone to dominant deleterious mutations and frequently implicated in cancer and genetic diseases. Hence, identifying ohnologs is central to better understand the evolution of vertebrates and their susceptibility to genetic diseases. Early computational analyses to identify vertebrate ohnologs relied on content-based synteny comparisons between the human genome and a single invertebrate outgroup genome or within the human genome itself. These approaches are thus limited by lineage specific rearrangements in individual genomes. We report, in this study, the identification of vertebrate ohnologs based on the quantitative assessment and integration of synteny conservation between six amniote vertebrates and six invertebrate outgroups. Such a synteny comparison across multiple genomes is shown to enhance the statistical power of ohnolog identification in vertebrates compared to earlier approaches, by overcoming lineage specific genome rearrangements. Ohnolog gene families can be browsed and downloaded for three statistical confidence levels or recompiled for specific, user-defined, significance criteria at http://ohnologs.curie.fr/. In the light of the importance of WGD on the genetic makeup of vertebrates, our analysis provides a useful resource for researchers interested in gaining further insights on vertebrate evolution and genetic diseases.

    View details for DOI 10.1371/journal.pcbi.1004394

    View details for Web of Science ID 000360620100035

    View details for PubMedID 26181593

  • A platform for rapid exploration of aging and diseases in a naturally short-lived vertebrate. Cell Harel, I., Benayoun, B. A., Machado, B., Singh, P. P., Hu, C., Pech, M. F., Valenzano, D. R., Zhang, E., Sharp, S. C., Artandi, S. E., Brunet, A. 2015; 160 (5): 1013-1026


    Aging is a complex process that affects multiple organs. Modeling aging and age-related diseases in the lab is challenging because classical vertebrate models have relatively long lifespans. Here, we develop the first platform for rapid exploration of age-dependent traits and diseases in vertebrates, using the naturally short-lived African turquoise killifish. We provide an integrative genomic and genome-editing toolkit in this organism using our de-novo-assembled genome and the CRISPR/Cas9 technology. We mutate many genes encompassing the hallmarks of aging, and for a subset, we produce stable lines within 2-3 months. As a proof of principle, we show that fish deficient for the protein subunit of telomerase exhibit the fastest onset of telomere-related pathologies among vertebrates. We further demonstrate the feasibility of creating specific genetic variants. This genome-to-phenotype platform represents a unique resource for studying vertebrate aging and disease in a high-throughput manner and for investigating candidates arising from human genome-wide studies.

    View details for DOI 10.1016/j.cell.2015.01.038

    View details for PubMedID 25684364

  • Human Dominant Disease Genes Are Enriched in Paralogs Originating from Whole Genome Duplication PLOS COMPUTATIONAL BIOLOGY Singh, P. P., Affeldt, S., Malaguti, G., Isambert, H. 2014; 10 (7)

    View details for DOI 10.1371/journal.pcbi.1003754

    View details for Web of Science ID 000339890900056

    View details for PubMedID 25080083

  • On the retention of gene duplicates prone to dominant deleterious mutations THEORETICAL POPULATION BIOLOGY Malaguti, G., Singh, P. P., Isambert, H. 2014; 93: 38-51


    Recent studies have shown that gene families from different functional categories have been preferentially expanded either by small scale duplication (SSD) or by whole-genome duplication (WGD). In particular, gene families prone to dominant deleterious mutations and implicated in cancers and other genetic diseases in human have been greatly expanded through two rounds of WGD dating back from early vertebrates. Here, we strengthen this intriguing observation, showing that human oncogenes involved in different primary tumors have retained many WGD duplicates compared to other human genes. In order to rationalize this evolutionary outcome, we propose a consistent population genetics model to analyze the retention of SSD and WGD duplicates taking into account their propensity to acquire dominant deleterious mutations. We solve a deterministic haploid model including initial duplicated loci, their retention through sub-functionalization or their neutral loss-of-function or deleterious gain-of-function at one locus. Extensions to diploid genotypes are presented and population size effects are analyzed using stochastic simulations. The only difference between the SSD and WGD scenarios is the initial number of individuals with duplicated loci. While SSD duplicates need to spread through the entire population from a single individual to reach fixation, WGD duplicates are de facto fixed in the small initial post-WGD population arising through the ploidy incompatibility between post-WGD individuals and the rest of the pre-WGD population. WGD duplicates prone to dominant deleterious mutations are then shown to be indirectly selected through purifying selection in post-WGD species, whereas SSD duplicates typically require positive selection. These results highlight the long-term evolution mechanisms behind the surprising accumulation of WGD duplicates prone to dominant deleterious mutations and are shown to be consistent with cancer genome data on the prevalence of human oncogenes with WGD duplicates.

    View details for DOI 10.1016/j.tpb.2014.01.004

    View details for Web of Science ID 000333727800004

    View details for PubMedID 24530892

  • Evolution and cancer: expansion of dangerous gene repertoire by whole genome duplications M S-MEDECINE SCIENCES Affeldt, S., Singh, P. P., Cascone, I., Selimoglu, R., Camonis, J., Isambert, H. 2013; 29 (4): 358-361

    View details for DOI 10.1051/medsci/2013294008

    View details for Web of Science ID 000318668300008

    View details for PubMedID 23621930

  • On the Expansion of "Dangerous'' Gene Repertoires by Whole-Genome Duplications in Early Vertebrates CELL REPORTS Singh, P. P., Affeldt, S., Cascone, I., Selimoglu, R., Camonis, J., Isambert, H. 2012; 2 (5): 1387-1398


    The emergence and evolutionary expansion of gene families implicated in cancers and other severe genetic diseases is an evolutionary oddity from a natural selection perspective. Here, we show that gene families prone to deleterious mutations in the human genome have been preferentially expanded by the retention of "ohnolog" genes from two rounds of whole-genome duplication (WGD) dating back from the onset of jawed vertebrates. We further demonstrate that the retention of many ohnologs suspected to be dosage balanced is in fact indirectly mediated by their susceptibility to deleterious mutations. This enhanced retention of "dangerous" ohnologs, defined as prone to autosomal-dominant deleterious mutations, is shown to be a consequence of WGD-induced speciation and the ensuing purifying selection in post-WGD species. These findings highlight the importance of WGD-induced nonadaptive selection for the emergence of vertebrate complexity, while rationalizing, from an evolutionary perspective, the expansion of gene families frequently implicated in genetic disorders and cancers.

    View details for DOI 10.1016/j.celrep.2012.09.034

    View details for Web of Science ID 000314457700032

    View details for PubMedID 23168259

  • Case for an RNA-prion world: a hypothesis based on conformational diversity JOURNAL OF BIOLOGICAL PHYSICS Singh, P. P., Banerji, A. 2011; 37 (2): 185-188


    Prions and other misfolded proteins can impart their structure and functions to normal molecules. Based upon a thorough structural assessment of RNA, prions and misfolded proteins, especially from the perspective of conformational diversity, we propose a case for co-existence of these in the pre-biotic world. Analyzing the evolution of physical aspects of biochemical structures, we put forward a case for an RNA-prion pre-biotic world, instead of, merely, the "RNA World".

    View details for DOI 10.1007/s10867-011-9219-7

    View details for Web of Science ID 000287929000002

    View details for PubMedID 22379228