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- Bradnam, K. R., et al.
(author)
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Assemblathon 2 : Evaluating de novo methods of genome assembly in three vertebrate species
- 2013
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In: GigaScience. - : BioMed Central (BMC). - 2047-217X. ; 2:1
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Journal article (peer-reviewed)abstract
- Background: The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results: In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions: Many current genome assemblers produced useful assemblies, containing a significant representation of their genes and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another.
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| 2. |
- Weinstock, Joshua S, et al.
(author)
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Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.
- 2023
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In: Nature. - 1476-4687. ; 616:7958, s. 755-763
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Journal article (peer-reviewed)abstract
- Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, butthis effect was not seen inclones withdriver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimentalknockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
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| 3. |
- Unick, J. L., et al.
(author)
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Four-Year Physical Activity Levels among Intervention Participants with Type 2 Diabetes
- 2016
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In: Medicine & Science in Sports & Exercise. - 0195-9131. ; 48:12, s. 2437-2445
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Journal article (peer-reviewed)abstract
- Physical activity (PA) has numerous health benefits, particularly for those with diabetes. However, rates of long-term PA participation are often poor. Purpose This study examined the effect of an intensive lifestyle intervention (ILI) on objectively assessed PA for a 4-yr period among older adults with type 2 diabetes. Methods Data from 2400 participants (age = 59.3 ± 6.9 yr, body mass index = 36.1 ± 5.9 kg·m-2) with accelerometry data from the Look AHEAD trial were included in the analyses. Participants randomized to ILI were instructed to reduce caloric intake and progress to ≥175 min·wk-1 of moderate-to-vigorous-intensity PA (MVPA), whereas those randomized to Diabetes Support and Education (DSE) served as the control group. PA was measured at baseline, year 1, and year 4 using an RT3 accelerometer, and bout-related MVPA (PA ≥3 METs, accumulated in bouts of ≥10 min in duration) was calculated. Results Despite no differences at baseline (ILI = 93.4 ± 152.7 vs DSE = 88.4 ± 143.6 min·wk-1), bout-related MVPA was significantly greater in ILI compared with DSE at year 1 (151.0 ± 213.5 vs 87.5 ± 145.1 min·wk-1, P < 0.0001) and year 4 (102.9 ± 195.6 vs 73.9 ± 267.5 min·wk-1, P < 0.001), and more ILI participants achieved ≥175 min·wk-1 at year 1 (29.1% vs 16.3%, P < 0.001) and year 4 (18.3% vs 10.0%, P < 0.001). Forty-one percent of ILI participants who achieved ≥175 min·wk-1 at year 1 maintained this threshold of PA at year 4. However, the majority of ILI participants never achieved the ≥175 min·wk-1 threshold. Conclusions When measured objectively and compared with DSE, ILI engaged in significantly more bout-related MVPA for a 4-yr period. However, future intervention strategies should target the large percentage of individuals who fail to reach the MVPA goal as result of a lifestyle intervention. © 2016 by the American College of Sports Medicine.
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| 4. |
- Unick, J. L., et al.
(author)
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Objectively Assessed Physical Activity and Weight Loss Maintenance among Individuals Enrolled in a Lifestyle Intervention
- 2017
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In: Obesity. - : Wiley. - 1930-7381. ; 25:11, s. 1903-1909
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Journal article (peer-reviewed)abstract
- Objective: To examine the relationship between objectively assessed moderate-to-vigorous intensity physical activity (MVPA) and 4-year weight loss (WL) and WL maintenance among individuals with diabetes enrolled in the Look AHEAD trial. Methods: MVPA was measured in a subgroup of lifestyle intervention participants with accelerometry data at baseline and at 1 and 4 years (n = 553; age: 59.7 ± 6.8 y; BMI: 35.5 ± 5.9 kg/m2). Minutes per week of bout-related MVPA were calculated (≥ 3 metabolic equivalents, ≥ 10-min bouts), and adherence to the national physical activity (PA) recommendation for WL maintenance (≥ 250 min/wk) was assessed. Results: Independent of 1-year WL, 4-year MVPA (β = −0.003, SE = 0.002, P = 0.006), but not 1-year MVPA (β = 0.0001, SE = 0.001, P = 0.50), was significantly associated with 4-year WL. Compared with “nonmaintainers” (≥ 10% WL at year 1, but < 10% at year 4; n = 132), WL maintainers (≥ 10% WL at years 1 and 4; n = 103) had higher MVPA at year 1 (253.4 ± 251.8 vs. 163.9 ± 158.2 min/wk, P = 0.002) and year 4 (155.3 ± 180.6 vs. 111.4 ± 154.5 min/wk, P = 0.046). Although 38.8% and 22.3% of WL maintainers engaged in ≥ 250 min/wk at years 1 and 4, respectively, many engaged in < 150 min/wk (year 1: 41%, year 4: 61%). Conclusions: Higher weekly MVPA is associated with greater long-term WL and weight maintenance; however, many individuals are able to maintain ≥ 10% WL while engaging in little MVPA. © 2017 The Obesity Society
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