Mutational signatures <i>in vivo</i>, <i>in vitro</i> and through reprogramming.

<p><b>a</b>. Schematic showing the longitudinal progression from <i>in vivo</i> development, <i>in vitro</i> culture of somatic cells through reprogramming and finally through to the experimental set-up used to calculate the mutation rate in iPSC maintenance culture. <b>b</b>. Mutational spectrum of SNVs found in the EPCs (top), and primary (middle) and sub-cloned (bottom) S7-RE14 iPSC lines. Clonal (left) and sub-clonal (right) mutations were shown separately. <b>c</b>. Contribution of mutational processes identified by the NNMF analysis. The germ line mutations described in ref 18 were analysed [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005932#pgen.1005932.ref018" target="_blank">18</a>]. The NNMF analysis was not performed for the mutations in sub-clonal S7-EPC due to the limited number of mutations available.</p

Mutation rate of human pluripotent cells in culture.

<p><b>a</b>. The mean numbers of SNVs accumulated during 60 cell divisions in 2 iPSC lines, S7-RE14 (<i>n</i> = 3) and S4-SF6 (<i>n</i> = 2) and a human ESC line H9 (<i>n</i> = 3). Data are shown as mean ± SD. <b>b</b>. Mutation rate per cell per division in each pluripotent cell line.</p

Summary of WGS and deep sequence analysis.

<p>Summary of WGS and deep sequence analysis.</p

Comparing acquired SNVs in iPSCs derived from a polyclonal or a monoclonal origin.

<p><b>a</b>. Schematic comparing the reprogramming of polyclonal and monoclonal cells. Polyclonal cells such as fibroblasts (left panel) give rise to iPSCs which do not share a majority of mutations since they are derived from different progenitors. In contrast, iPSCs derived from monoclonal cells (right panel) such as EPCs share a proportion of their mutations and carry private mutations specific to each line. <b>b, c</b>. Exome sequencing of iPSCs generated using fibroblasts from two different individuals, a 65-year-old alpha-1 antitrypsin deficiency patient (AATD) (<b>b</b>) and a healthy subject, S2 (<b>c</b>). The data for iPSC-B were taken from our previous work [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005932#pgen.1005932.ref011" target="_blank">11</a>]. Each column represents one SNV in the indicated gene. Duplicated genes indicate two adjacent SNVs. Green, mutation absent; pink, mutation present. See <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005932#pgen.1005932.s004" target="_blank">S2</a> and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005932#pgen.1005932.s005" target="_blank">S3</a> Tables for the complete description. <b>d, e</b>. Exome sequencing of iPSC lines generated using monoclonal EPCs from the same AATD patient in <b>b</b> as well as a healthy subject, S7 (<b>e</b>). Orange, mutation detected by amplicon resequencing. See <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005932#pgen.1005932.s006" target="_blank">S4</a> and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005932#pgen.1005932.s007" target="_blank">S5</a> Tables for the complete description.</p

Eagle-i record-level citation widget.

<p>Eagle-i record-level citation widget.</p

Record-level versioning and release-level versioning.

<p>Record-level versioning and release-level versioning.</p

A summary of the 10 recommendations and their direct or indirect impact on different kinds of identifier roles.

<p>A summary of the 10 recommendations and their direct or indirect impact on different kinds of identifier roles.</p

Anatomy of a web-based identifier.

<p>An example of an exemplary unique resource identifier (URI) is below; it is comprised of American Standard Code for Information Interchange (ASCII) characters and follows a pattern that starts with a fixed set of characters (URI pattern). That URI pattern is followed by a local identifier (local ID)—an identifier which, by itself, is only guaranteed to be locally unique within the database or source. A local ID is sometimes referred to as an “accession.” Note this figure illustrates the simplest representation; nuances regarding versioning are covered in Lesson 6 and <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2001414#pbio.2001414.g005" target="_blank">Fig 5</a>.</p

Desirable characteristics for database identifiers in the life sciences.

<p>Desirable characteristics for database identifiers in the life sciences.</p

Contributions and roles related to content as they correspond to identifier creation versus identifier reuse.

<p>The decision about whether to create a new identifier or reuse an existing one depends on the role you play in the creation, editing, and republishing of content; for certain roles (and when several roles apply) that decision is a judgement call. Asterisks convey cases in which the best course of action is often to correct/improve the original record in collaboration with the original source; the guidance about identifier creation versus reuse is meant to apply only when such collaboration is not practicable (and an alternate record is created). It is common that a given actor may have multiple roles along this spectrum; for instance, a given record in monarchinitiative.org may reflect a combination of (a) corrections Monarch staff made in collaboration with the original data source, (b) post-ingest curation by Monarch staff, (c) expanded content integrated from multiple sources.</p