The Algorithmic Origins of Life

Although it has been notoriously difficult to pin down precisely what it is that makes life so distinctive and remarkable, there is general agreement that its informational aspect is one key property, perhaps the key property. The unique informational narrative of living systems suggests that life may be characterized by context-dependent causal influences, and in particular, that top-down (or downward) causation -- where higher-levels influence and constrain the dynamics of lower-levels in organizational hierarchies -- may be a major contributor to the hierarchal structure of living systems. Here we propose that the origin of life may correspond to a physical transition associated with a shift in causal structure, where information gains direct, and context-dependent causal efficacy over the matter it is instantiated in. Such a transition may be akin to more traditional physical transitions (e.g. thermodynamic phase transitions), with the crucial distinction that determining which phase (non-life or life) a given system is in requires dynamical information and therefore can only be inferred by identifying causal architecture. We discuss some potential novel research directions based on this hypothesis, including potential measures of such a transition that may be amenable to laboratory study, and how the proposed mechanism corresponds to the onset of the unique mode of (algorithmic) information processing characteristic of living systems.Comment: 13 pages, 1 tabl

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Dust measurements in the coma of comet 67P/Churyumov-Gerasimenko inbound to the Sun

Critical measurements for understanding accretion and the dust/gas ratio in the solar nebula, where planets were forming 4.5 billion years ago, are being obtained by the GIADA (Grain Impact Analyser and Dust Accumulator) experiment on the European Space Agency’s Rosetta spacecraft orbiting comet 67P/Churyumov-Gerasimenko. Between 3.6 and 3.4 astronomical units inbound, GIADA and OSIRIS (Optical, Spectroscopic, and Infrared Remote Imaging System) detected 35 outflowing grains of mass 10−10 to 10−7 kilograms, and 48 grains of mass 10−5 to 10−2 kilograms, respectively. Combined with gas data from the MIRO (Microwave Instrument for the Rosetta Orbiter) and ROSINA (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) instruments, we find a dust/gas mass ratio of 4 ± 2 averaged over the sunlit nucleus surface. A cloud of larger grains also encircles the nucleus in bound orbits from the previous perihelion.The largest orbiting clumps are meter-sized, confirming the dust/gas ratio of 3 inferred at perihelion from models of dust comae and trails

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that -80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAFPeer reviewe

BLUEPRINT to decode the epigenetic signature written in blood

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