docs: add bib and citation example

documentation/apa-sequencing.bib

@@ -0,0 +1,142 @@
+
+@article{wu_somatic_2023,
+	title = {Somatic mutations of {CADM1} in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production},
+	volume = {55},
+	issn = {1546-1718},
+	doi = {10.1038/s41588-023-01403-0},
+	abstract = {Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1. Independent whole exome sequencing of 40 and 81 APAs found intramembranous p.Val380Asp or p.Gly379Asp variants in two patients whose hypertension and periodic primary aldosteronism were cured by adrenalectomy. Replication identified two more APAs with each variant (total, n = 6). The most upregulated gene (10- to 25-fold) in human adrenocortical H295R cells transduced with the mutations (compared to wildtype) was CYP11B2 (aldosterone synthase), and biological rhythms were the most differentially expressed process. CADM1 knockdown or mutation inhibited gap junction (GJ)-permeable dye transfer. GJ blockade by Gap27 increased CYP11B2 similarly to CADM1 mutation. Human adrenal zona glomerulosa (ZG) expression of GJA1 (the main GJ protein) was patchy, and annular GJs (sequelae of GJ communication) were less prominent in CYP11B2-positive micronodules than adjacent ZG. Somatic mutations of CADM1 cause reversible hypertension and reveal a role for GJ communication in suppressing physiological aldosterone production.},
+	language = {eng},
+	number = {6},
+	journal = {Nature Genetics},
+	author = {Wu, Xilin and Azizan, Elena A. B. and Goodchild, Emily and Garg, Sumedha and Hagiyama, Man and Cabrera, Claudia P. and Fernandes-Rosa, Fabio L. and Boulkroun, Sheerazed and Kuan, Jyn Ling and Tiang, Zenia and David, Alessia and Murakami, Masanori and Mein, Charles A. and Wozniak, Eva and Zhao, Wanfeng and Marker, Alison and Buss, Folma and Saleeb, Rebecca S. and Salsbury, Jackie and Tezuka, Yuta and Satoh, Fumitoshi and Oki, Kenji and Udager, Aaron M. and Cohen, Debbie L. and Wachtel, Heather and King, Peter J. and Drake, William M. and Gurnell, Mark and Ceral, Jiri and Ryska, Ales and Mustangin, Muaatamarulain and Wong, Yin Ping and Tan, Geok Chin and Solar, Miroslav and Reincke, Martin and Rainey, William E. and Foo, Roger S. and Takaoka, Yutaka and Murray, Sandra A. and Zennaro, Maria-Christina and Beuschlein, Felix and Ito, Akihiko and Brown, Morris J.},
+	month = jun,
+	year = {2023},
+	pmid = {37291193},
+	pmcid = {PMC10260400},
+	keywords = {Humans, Hypertension, Mutation, Adrenal Cortex Neoplasms, Adrenocortical Adenoma, Aldosterone, Cell Adhesion Molecule-1, Cytochrome P-450 CYP11B2, Gap Junctions, Hyperaldosteronism},
+	pages = {1009--1021},
+	file = {Volltext:C\:\\Users\\bernt\\Zotero\\storage\\6Q4LH5YH\\Wu et al. - 2023 - Somatic mutations of CADM1 in aldosterone-producin.pdf:application/pdf},
+}
+
+@article{nanba_somatic_2020,
+	title = {Somatic {CACNA1H} {Mutation} {As} a {Cause} of {Aldosterone}-{Producing} {Adenoma}},
+	volume = {75},
+	issn = {1524-4563},
+	doi = {10.1161/HYPERTENSIONAHA.119.14349},
+	abstract = {Driver somatic mutations for aldosterone excess have been found in ≈90\% of aldosterone-producing adenomas (APAs) using an aldosterone synthase (CYP11B2)-guided sequencing approach. In the present study, we identified a novel somatic CACNA1H mutation (c.T4289C, p.I1430T) in an APA without any currently known aldosterone-driver mutations using CYP11B2 immunohistochemistry-guided whole exome sequencing. The CACNA1H gene encodes a voltage-dependent T-type calcium channel alpha-1H subunit. Germline variants in this gene are known as a cause of familial hyperaldosteronism IV. Targeted next-generation sequencing detected identical CACNA1H variants in 2 additional APAs in a cohort of the University of Michigan, resulting in a prevalence of 4\% (3/75) in APAs. We tested the functional effect of the variant on adrenal cell aldosterone production and CYP11B2 mRNA expression using the human adrenocortical HAC15 cell line with a doxycycline-inducible CACNA1HI1430T mutation. Doxycycline treatment increased CYP11B2 mRNA levels as well as aldosterone production, supporting a pathological role of the CACNA1H p.I1430T mutation on the development of primary aldosteronism. In conclusion, somatic CACNA1H mutation is a genetic cause of APAs. Although the prevalence of this mutation is low, this study will provide better understanding of molecular mechanism of inappropriate aldosterone production in APAs.},
+	language = {eng},
+	number = {3},
+	journal = {Hypertension (Dallas, Tex.: 1979)},
+	author = {Nanba, Kazutaka and Blinder, Amy R. and Rege, Juilee and Hattangady, Namita G. and Else, Tobias and Liu, Chia-Jen and Tomlins, Scott A. and Vats, Pankaj and Kumar-Sinha, Chandan and Giordano, Thomas J. and Rainey, William E.},
+	month = mar,
+	year = {2020},
+	pmid = {31983310},
+	pmcid = {PMC7059016},
+	keywords = {Humans, Mutation, Mutation, Missense, High-Throughput Nucleotide Sequencing, RNA, Messenger, Exome Sequencing, Cell Line, Tumor, Recombinant Proteins, RNA, Neoplasm, Genetic Vectors, Adrenal Cortex Neoplasms, Aldosterone, Cytochrome P-450 CYP11B2, Hyperaldosteronism, Adenoma, Aldosterone-producing adenoma, Angiotensin II, Calcium channel, Calcium Channels, T-Type, Calcium Signaling, CYP11B2, Doxycycline, Enzyme Induction, Lentivirus, Primary aldosteronism},
+	pages = {645--649},
+	file = {Volltext:C\:\\Users\\bernt\\Zotero\\storage\\6ZHVTYV6\\Nanba et al. - 2020 - Somatic CACNA1H Mutation As a Cause of Aldosterone.pdf:application/pdf},
+}
+
+@article{zhou_somatic_2021,
+	title = {Somatic mutations of {GNA11} and {GNAQ} in {CTNNB1}-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause},
+	volume = {53},
+	issn = {1546-1718},
+	doi = {10.1038/s41588-021-00906-y},
+	abstract = {Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59\%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1.},
+	language = {eng},
+	number = {9},
+	journal = {Nature Genetics},
+	author = {Zhou, Junhua and Azizan, Elena A. B. and Cabrera, Claudia P. and Fernandes-Rosa, Fabio L. and Boulkroun, Sheerazed and Argentesi, Giulia and Cottrell, Emily and Amar, Laurence and Wu, Xilin and O'Toole, Sam and Goodchild, Emily and Marker, Alison and Senanayake, Russell and Garg, Sumedha and Åkerström, Tobias and Backman, Samuel and Jordan, Suzanne and Polubothu, Satyamaanasa and Berney, Daniel M. and Gluck, Anna and Lines, Kate E. and Thakker, Rajesh V. and Tuthill, Antoinette and Joyce, Caroline and Kaski, Juan Pablo and Karet Frankl, Fiona E. and Metherell, Lou A. and Teo, Ada E. D. and Gurnell, Mark and Parvanta, Laila and Drake, William M. and Wozniak, Eva and Klinzing, David and Kuan, Jyn Ling and Tiang, Zenia and Gomez Sanchez, Celso E. and Hellman, Per and Foo, Roger S. Y. and Mein, Charles A. and Kinsler, Veronica A. and Björklund, Peyman and Storr, Helen L. and Zennaro, Maria-Christina and Brown, Morris J.},
+	month = sep,
+	year = {2021},
+	pmid = {34385710},
+	pmcid = {PMC9082578},
+	keywords = {Humans, Female, Male, Adult, Adolescent, Middle Aged, Pregnancy, Adrenal Cortex Neoplasms, Adrenocortical Adenoma, Aldosterone, Hyperaldosteronism, beta Catenin, GTP-Binding Protein alpha Subunits, GTP-Binding Protein alpha Subunits, Gq-G11, Menopause, Puberty},
+	pages = {1360--1372},
+	file = {Akzeptierte Version:C\:\\Users\\bernt\\Zotero\\storage\\R9H6IKJ2\\Zhou et al. - 2021 - Somatic mutations of GNA11 and GNAQ in CTNNB1-muta.pdf:application/pdf},
+}
+
+@article{backman_rna_2019,
+	title = {{RNA} {Sequencing} {Provides} {Novel} {Insights} into the {Transcriptome} of {Aldosterone} {Producing} {Adenomas}},
+	volume = {9},
+	issn = {2045-2322},
+	url = {https://www.nature.com/articles/s41598-019-41525-2},
+	doi = {10.1038/s41598-019-41525-2},
+	abstract = {Abstract
+            
+              Aldosterone producing adenomas (APAs) occur in the adrenal glands of around 30\% of patients with primary aldosteronism, the most common form of secondary hypertension. Somatic mutations in
+              KCNJ5
+              ,
+              ATP1A1
+              ,
+              ATP2B3
+              ,
+              CACNA1D
+              and
+              CTNNB1
+              have been described in {\textasciitilde}60\% of these tumours. We subjected 15 aldosterone producing adenomas (13 with known mutations and two without) to RNA Sequencing and Whole Genome Sequencing (n = 2). All known mutations were detected in the RNA-Seq reads, and mutations in
+              ATP2B3
+              (G123R) and
+              CACNA1D
+              (S410L) were discovered in the tumours without known mutations. Adenomas with
+              CTNNB1
+              mutations showed a large number of differentially expressed genes (1360 compared to 106 and 75 for
+              KCNJ5
+              and
+              ATP1A1
+              /
+              ATP2B3
+              respectively) and clustered together in a hierarchical clustering analysis. RT-PCR in an extended cohort of 49 APAs confirmed higher expression of
+              AFF3
+              and
+              ISM1
+              in APAs with
+              CTNNB1
+              mutations. Investigation of the expression of genes involved in proliferation and apoptosis revealed subtle differences between tumours with and without
+              CTNNB1
+              mutations. Together our results consolidate the notion that
+              CTNNB1
+              mutations characterize a distinct subgroup of APAs.},
+	language = {en},
+	number = {1},
+	urldate = {2023-10-16},
+	journal = {Scientific Reports},
+	author = {Backman, Samuel and Åkerström, Tobias and Maharjan, Rajani and Cupisti, Kenko and Willenberg, Holger S. and Hellman, Per and Björklund, Peyman},
+	month = apr,
+	year = {2019},
+	pages = {6269},
+	file = {Volltext:C\:\\Users\\bernt\\Zotero\\storage\\6D949H3D\\Backman et al. - 2019 - RNA Sequencing Provides Novel Insights into the Tr.pdf:application/pdf},
+}
+
+@article{choi_k_2011,
+	title = {K $^{\textrm{+}}$ {Channel} {Mutations} in {Adrenal} {Aldosterone}-{Producing} {Adenomas} and {Hereditary} {Hypertension}},
+	volume = {331},
+	issn = {0036-8075, 1095-9203},
+	url = {https://www.science.org/doi/10.1126/science.1198785},
+	doi = {10.1126/science.1198785},
+	abstract = {Potassium channel mutations drive both cell growth and hormone production in an adrenal tumor that causes severe hypertension.
+          , 
+            
+              Endocrine tumors such as aldosterone-producing adrenal adenomas (APAs), a cause of severe hypertension, feature constitutive hormone production and unrestrained cell proliferation; the mechanisms linking these events are unknown. We identify two recurrent somatic mutations in and near the selectivity filter of the potassium (K
+              +
+              ) channel KCNJ5 that are present in 8 of 22 human APAs studied. Both produce increased sodium (Na
+              +
+              ) conductance and cell depolarization, which in adrenal glomerulosa cells produces calcium (Ca
+              2+
+              ) entry, the signal for aldosterone production and cell proliferation. Similarly, we identify an inherited
+              KCNJ5
+              mutation that produces increased Na
+              +
+              conductance in a Mendelian form of severe aldosteronism and massive bilateral adrenal hyperplasia. These findings explain pathogenesis in a subset of patients with severe hypertension and implicate loss of K
+              +
+              channel selectivity in constitutive cell proliferation and hormone production.},
+	language = {en},
+	number = {6018},
+	urldate = {2024-05-30},
+	journal = {Science},
+	author = {Choi, Murim and Scholl, Ute I. and Yue, Peng and Björklund, Peyman and Zhao, Bixiao and Nelson-Williams, Carol and Ji, Weizhen and Cho, Yoonsang and Patel, Aniruddh and Men, Clara J. and Lolis, Elias and Wisgerhof, Max V. and Geller, David S. and Mane, Shrikant and Hellman, Per and Westin, Gunnar and Åkerström, Göran and Wang, Wenhui and Carling, Tobias and Lifton, Richard P.},
+	month = feb,
+	year = {2011},
+	pages = {768--772},
+	file = {Volltext:C\:\\Users\\bernt\\Zotero\\storage\\ZT9AWKCR\\Choi et al. - 2011 - K + Channel Mutations in Adrenal Aldost.pdf:application/pdf},
+}

documentation/index.Rmd

@@ -24,7 +24,7 @@ This documentation is intended to describe the [apa-sequencing](https://github.c
 
 ## Objective {-}
 
-Primary aldosteronism (PA) is the most common cause of secondary hypertension and is more common than primary hypertension in causing secondary diseases such as stroke, myocardial infarction, heart and renal failure. It is caused by inappropriately increased, partially autonomous synthesis and secretion of the steroid hormone aldosterone with consequent increased renal and intestinal sodium and water reabsorption and increased potassium secretion. The most common causes are a unilateral benign adrenal tumour (aldosterone-producing adenoma, APA) or bilateral aldosteronism. In recent years, the molecular mechanisms leading to autonomous aldosterone production have become the focus of increasing scientific attention. It has been shown that approximately 95% of all APAs have somatic mutations in known disease genes, mainly affecting ion channels and transporters: About 40% have *KCNJ5* mutations; *CACNA1D* is the second most commonly affected gene (about 20%). Other less common somatic mutations include mutations in the ATPases *ATP1A1* and *ATP2B3* and the gene encoding b-catenin, *CTNNB1*.
+Primary aldosteronism (PA) is the most common cause of secondary hypertension and is more common than primary hypertension in causing secondary diseases such as stroke, myocardial infarction, heart and renal failure. It is caused by inappropriately increased, partially autonomous synthesis and secretion of the steroid hormone aldosterone with consequent increased renal and intestinal sodium and water reabsorption and increased potassium secretion. The most common causes are a unilateral benign adrenal tumour (aldosterone-producing adenoma, APA) or bilateral aldosteronism. In recent years, the molecular mechanisms leading to autonomous aldosterone production have become the focus of increasing scientific attention. It has been shown that approximately 95% of all APAs have somatic mutations in known disease genes, mainly affecting ion channels and transporters: About 40% have *KCNJ5* (e.g. [@choi_k_2011]) mutations; *CACNA1D* is the second most commonly affected gene (about 20%). Other less common somatic mutations include mutations in the ATPases *ATP1A1* and *ATP2B3* and the gene encoding b-catenin, *CTNNB1*.
 
 ## Methods {-}