{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:21:25Z","timestamp":1790425285514,"version":"4.1.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Detecting selection in B cell Ig sequences is critical to understanding affinity maturation and can provide insights into Ag-driven selection in normal and pathologic immune responses. The most common sequence-based methods for detecting selection analyze the ratio of replacement and silent mutations using a binomial statistical analysis. However, these approaches have been criticized for low sensitivity. An alternative method is based on the analysis of lineage trees constructed from sets of clonally related Ig sequences. Several tree shape measures have been proposed as indicators of selection that can be statistically compared across cohorts. However, we show that tree shape analysis is confounded by underlying experimental factors that are difficult to control for in practice, including the sequencing depth and number of generations in each clone. Thus, although lineage tree shapes may reflect selection, their analysis alone is an unreliable measure of in vivo selection. To usefully capture the information provided by lineage trees, we propose a new method that applies the binomial statistical framework to mutations identified based on lineage tree structure. This hybrid method is able to detect selection with increased sensitivity in both simulated and experimental data sets. We anticipate that this approach will be especially useful in the analysis of large-scale Ig sequencing data sets generated by high-throughput sequencing technologies.<\/jats:p>","DOI":"10.4049\/jimmunol.1301551","type":"journal-article","created":{"date-parts":[[2013,12,28]],"date-time":"2013-12-28T03:47:11Z","timestamp":1388202431000},"page":"867-874","source":"Crossref","is-referenced-by-count":34,"title":["Integrating B Cell Lineage Information into Statistical Tests for Detecting Selection in Ig Sequences"],"prefix":"10.1093","volume":"192","author":[{"given":"Mohamed","family":"Uduman","sequence":"first","affiliation":[{"name":"Interdepartmental Program in Computational Biology and Bioinformatics, Yale University , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J","family":"Shlomchik","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Vigneault","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School , Boston, MA 02115"},{"name":"AbVitro, Inc. , Boston, MA 02116"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George M","family":"Church","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven H","family":"Kleinstein","sequence":"additional","affiliation":[{"name":"Interdepartmental Program in Computational Biology and Bioinformatics, Yale University , New Haven, CT 06520"},{"name":"Department of Pathology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,2,1]]},"reference":[{"key":"2025032404105117900_r1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/276785a0","article-title":"Rearrangement of genetic information may produce immunoglobulin diversity","volume":"276","author":"Weigert","year":"1978","journal-title":"Nature"},{"key":"2025032404105117900_r2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/283497a0","article-title":"The joining of V and J gene segments creates antibody diversity","volume":"283","author":"Weigert","year":"1980","journal-title":"Nature"},{"key":"2025032404105117900_r3","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/302575a0","article-title":"Somatic generation of antibody diversity","volume":"302","author":"Tonegawa","year":"1983","journal-title":"Nature"},{"key":"2025032404105117900_r4","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.it.2006.06.007","article-title":"Why do B cells mutate their immunoglobulin receptors?","volume":"27","author":"Longo","year":"2006","journal-title":"Trends Immunol."},{"key":"2025032404105117900_r5","doi-asserted-by":"crossref","first-page":"3180","DOI":"10.1073\/pnas.81.10.3180","article-title":"Generation of antibody diversity in the immune response of BALB\/c mice to influenza virus hemagglutinin","volume":"81","author":"McKean","year":"1984","journal-title":"Proc. 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